[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"diffuse-midline-glioma-h3-k27m-mutant\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:diffuse-midline-glioma-h3-k27m-mutant":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,19,0,[8,47,87,112,132,157,184,218,249,274,306,332,374,412,451,470,495,517,543],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100440030","phase-2-combination-therapy-for-the-treatment-of-diffuse-midline-gliomas-100440030",false,"NCT05009992","Combination Therapy for the Treatment of Diffuse Midline Gliomas","A Combination Therapy Trial Using an Adaptive Platform Design for Children and Young Adults With Diffuse Midline Gliomas (DMGs) Including Diffuse Intrinsic Pontine Gliomas (DIPGs) at Initial Diagnosis, Post-Radiation Therapy and at Time of Progression","PNOC022","--COHORTS 1, 2, AND 3 CLOSED---\n\nINCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* New diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 1B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma Histone 3 lysine 27 - mutant (H3K27M); World Health Organization (WHO) grade III and IV H3 wildtype gliomas.\n* Must be within 6 weeks of diagnosis to begin standard of care radiation therapy on study.\n\nCOHORT 2A AND 2B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In Cohort 2B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n\nCOHORT 3A AND 3B:\n\n* Diagnosis of recurrent DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors, who have complete standard-of-care radiation therapy. In cohort 3B, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG including diffuse midline glioma H3K27M mutant; WHO grade III and IV H3 wildtype gliomas.\n* Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 4A AND 4B:\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 4B\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n\nCohort 4A\\^1 and 4B\\^1 (participants with newly diagnosed DMG prior to radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 4A\\^2 and 4B\\^2 (participants with newly diagnosed DMG who have completed radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 4A\\^3 and 4B\\^3 (participants with DMG at progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nCOHORT 5\n\n* Diagnosis of DMG with imaging and\u002For pathology consistent with a DMG, including spinal cord tumors. In cohort 5\\^1, previous tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG diffuse midline glioma H3K27-altered.\n* Not currently eligible for any other clinical trials that include administration of ONC201.\n* Multifocal and leptomeningeal disease will be eligible for Cohort 5.\n* Participant's tumor must demonstrate one of the following molecular alterations considered targetable by an approved agent:\n\n  * BRAFV600E\n  * PDGFRA (DNA point mutation or amplification with \\>=5 copy numbers)\n  * FGFR1 (DNA point mutation, gene fusions, or amplification with \\>=5 copy numbers)\n  * NF1\n\nCohort 5\\^1 (participants pre-radiation): Must be able to begin standard of care radiation therapy on study within 6 weeks of diagnosis.\n\nCohort 5\\^2 (participants post-radiation): Participants must be within 4-14 weeks of completion of radiation and not have received additional therapy beyond completion of radiation therapy. Radiation should have started within 6 weeks of diagnosis.\n\nCohort 5\\^3 (participants with progression): Participants must have evidence of progression and not have received any treatment for this progression and have not previously received re-irradiation.\n\nAll Cohorts (except Cohort 6):\n\n* Age 2 to 39 years\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Any number of prior therapies are allowed.\n* Prior ONC201 exposure is allowed, except in participants who have participated in Chimerix trials investigating ONC201 in the upfront setting. Participants who participated in trials investigating ONC201 in the upfront setting will not be eligible at any time, with the exception if participants received ONC201 as part of PNOC022 or other expanded access programs such as German sources of ONC201.\n* Participant body weight must be above the minimum necessary for the participant to receive ONC201 (at least 10 kilograms (kg))\n* From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (21 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n\n  o The use of bevacizumab to control radiation therapy-induced edema is allowed (if used for tumor-directed therapy, please see required time period above).\n  * Dosing limitations are as follows:\n  * \\* Bevacizumab (or equivalent) for up to a maximum of 5 doses, dosing per institutional standard. There is no required washout period.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) or dexamethasone is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to beginning the agent.\n* Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm\\^3 (1.0g\u002Fl) AND\n  * Platelet count \\>= 75,000\u002Fmm\\^3 (100x10\\^9\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n  * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \\>= 70 mL\u002Fmin\u002F1.73 m\\^2 OR\n  * A serum creatinine within the normal limits for age\n  * Bilirubin (sum of conjugated + unconjugated) =\\\u003C 1.5 x upper limit of normal (ULN) for age AND\n  * Serum glutamate pyruvate transaminase (SGPT)(alanine aminotransferase (ALT)) =\\\u003C 3 x ULN AND\n  * Serum albumin \\>= 2 g\u002FDl\n  * No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of \\> 92% while breathing room air.\n  * Diarrhea \\\u003C grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * ECG must be obtained to verify the Corrected QT Interval (QTc). If an abnormal reading is obtained, the ECG should be repeated in triplicate. QTC \\\u003C 470 msec.\n  * Participants with history of congestive heart failure, at risk of having or have underlying cardiovascular disease, or with history of exposure to cardiotoxic drugs must have adequate cardiac function as determined by echocardiogram. Shortening fraction of \\>= 27%.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled\n* Females of child-bearing potential and males must agree to use adequate contraception.\n* Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants =\\\u003C 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Frozen tissue is also acceptable.\n\nCOHORT 6 Inclusion Criteria:\n\n* Diagnosis of newly diagnosed thalamic or pontine located DMG with imaging and\u002For pathology consistent with a DMG, excluding spinal cord tumors, who have completed standard-of-care radiation therapy. If archival tissue is available prior to first biopsy, participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required.\n* Participants must be within 4-14 weeks of completion of radiation. Radiation should have started within 6 weeks of diagnosis.\n* Age 2-39 years.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) is allowed. Any other agent given throughout radiation therapy must be discussed with the study chairs prior to enrollment.\n* Participants must have recovered from all acute side effects of prior therapy and be beyond the window for expected ongoing acute toxicities. Washout requirements from prior therapy include:\n\n  * At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 30 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies (28 days for bevacizumab when used for tumor-directed therapy, guidance on use for pseudo-progression is below), or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n  * At least 4 weeks prior to study enrollment from last immune therapy\n* Corticosteroids: Participants treated with corticosteroids must be on stable or decreasing dose for at least 1 week prior to enrollment, with maximum dexamethasone dose 0.1 mg\u002Fkg\u002Fday dexamethasone equivalent at time of enrollment.\n* The participant must have adequate organ function defined as:\n\n  * Peripheral absolute neutrophil count (ANC) \\>= 750\u002Fmm3 (1.0g\u002Fl) and\n  * Platelet count \\>= 75,000\u002Fmm3 (100x109\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment.\n  * Creatinine clearance or radioisotope GFR \\>= 70mL\u002Fmin\u002F1.73 m2 or\n  * A serum creatinine within the normal limits for age.\n  * Total bilirubin \\\u003C= 3 x upper limit of normal (ULN); in presence of Gilbert's syndrome, total bilirubin \\\u003C\u002F= 6 x ULN or direct bilirubin \\\u003C= 3 x ULN\n  * ALT \\\u003C= 5 x ULN\n  * AST \\\u003C= 5 x ULN.\n  * Serum albumin \\>= 2 g\u002FdL\n  * Diarrhea \\\u003C grade 2 by CTCAE v5.0.\n  * No history of congestive heart failure or family history of long QT syndrome.\n  * Participants with seizure disorder may be enrolled if seizure disorder is well controlled.\n* The effects of the study drugs on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception.\n* Karnofsky \\>\u002F= 70 for Participants \\> 16 years of age and Lansky \\>\u002F= 70 for participants \\\u003C\u002F= 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n\nEXCLUSION CRITERIA:\n\nCOHORT 1A AND 1B:\n\n* Prior exposure to radiation therapy.\n* Thalamic and Cerebellar H3K27M DMG.\n\nCOHORT 2A AND 2B:\n\n* For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply:\n* Thalamic and Cerebellar H3K27M DMG that has undergone standard radiation without concurrent therapy (other than temozolomide).\n\nCOHORT 1A AND 2A:\n\n• Deemed not appropriate for tissue resection\u002Fbiopsy.\n\nCOHORT 3A AND 3B:\n\n* Prior exposure to re-irradiation for tumor progression.\n* Thalamic and cerebellar H3K27M mutant DMG.\n\nCOHORT 4A AND 4B:\n\nCohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 4A\\^1and 4B\\^1: Prior exposure to radiation therapy\n* Cohort 4A\\^3 and 4B\\^3: Prior exposure to re-irradiation for tumor progression\n\nCOHORT 5:\n\n* Thalamic and cerebellar H3K27M mutant DMG, except those who received ONC201\u002FONC026 from alternative source prior to 2024 or US patients enrolled while the accelerated approval new drug application for dordaviprone to treat recurrent H3 K27M-mutant diffuse glioma is under review by US FDA.\n* Cohort 5\\^1: Prior exposure to radiation therapy\n* Cohort 5\\^3: Prior exposure to re-irradiation for tumor progression\n\nAll Cohorts (except Cohort 6):\n\n* Diagnosis of a histone H3 wildtype grade II diffuse astrocytoma.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants who are currently receiving other anti-cancer agents.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.\n* Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination, with the exception of Cohort 5.\n* Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.\n* Concomitant use of potent CYP3A4\u002F5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.\n* Concomitant use of potent CYP3A4\u002F5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids is allowed.\n\nCOHORT 6 Exclusion Criteria:\n\n* • DMGs located outside the thalamus and pons including bilateral thalamic tumors.\n* Unacceptable anesthesia or surgery risk, as determined by the anesthesiologist or the neurosurgeon.\n* Evidence of significant mass effect\n* Evidence of herniation on imaging.\n* Participants with a known history coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of registration.\n* Participants must not require systemic anti-coagulation that cannot be halted for each intraoperative and perioperative biopsy time-period.\n* Participants with active viral infection or who are currently receiving antiviral treatment.\n* Participants with active, known, or suspected immunosuppressive disorders, such as acquired or congenital immune deficiency syndromes and autoimmune diseases.\n* This virus infects cells with a deficit in the RB gene. Therefore, participants with Li-Fraumeni Syndrome or a known germ line deficit in the retinoblastoma gene or its related pathway are excluded.\n* Participants must not have live or live-attenuated vaccinations within 30 days prior to DNX-2401 administration and while participating in the study. Killed vaccines are permitted.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the study chairs.\n* Participants with a known disorder that affects their immune system, such as HIV or Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants who are currently using inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from the study but need to be discussed with the study chair(s).\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in the study.\n* Evidence of disseminated disease, including multi-focal disease, diffuse leptomeningeal disease or CSF dissemination.","ALL","2 Years","39 Years",{"count":21,"type":22},360,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","This phase II trial determines if the combination of ONC201 with different drugs is effective for treating participants with diffuse midline gliomas (DMGs). Despite years of research, little to no progress has been made to improve outcomes for participants with DMGs, and there are few treatment options. This trial will utilize an adaptive platform design in that the different treatment arms for each cohort will be opened and closed based on ongoing preclinical investigation as well as evolving outcome data from the trial.\n\nNovel agents will be continuously added to this study as pre-clinical data emerge to suggest additive or synergistic activity when combined ONC201. Should a novel agent not have an RP2D at the time of incorporation into this study, a phase 1 lead-in will be performed prior to initiation of combination therapy (via study amendment).",[28,29,30,31,32,33],"Diffuse Intrinsic Pontine Glioma","Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent Diffuse Intrinsic Pontine Glioma","Recurrent Diffuse Midline Glioma, H3 K27M-Mutant","Recurrent WHO Grade III Glioma","WHO Grade III Glioma","RECRUITING","2026-06-23",{"date":37,"type":38},"2026-06-26","ACTUAL",{"date":40,"type":38},"2021-10-20",{"date":42,"type":22},"2029-06-30",{"name":44,"class":45},"University of California, San Francisco","OTHER",32,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":17,"minAge":54,"maxAge":19,"enrollmentInfo":55,"targetDuration":4,"studyType":23,"phases":57,"briefSummary":58,"conditions":59,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":76,"lastUpdatePostDateStruct":77,"startDateStruct":79,"completionDateStruct":81,"leadSponsor":83,"locationsCount":86},"100528530","phase-2-study-of-olutasidenib-and-temozolomide-in-hgg-100528530","NCT06161974","Study of Olutasidenib and Temozolomide in HGG","Phase 2 Study of Olutasidenib With Temozolomide as Maintenance Therapy in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG), Which Harbor IDH1 Mutations","Criteria TarGeT-D study strata definitions\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 3.\n* Stratum B: Patients with localized, intracranial, non-pontine, and non-thalamic IDH 1 mutant Astrocytoma, CNS WHO Grade 4.\n* Stratum C: Patients with IDH-1 mutant DIPG, primary thalamic and spinal cord IDH-1 mutant HGG.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR 1.2) Diagnosis:\n   * Patients with a newly-diagnosed IDH1-mutant HGG including DIPG are eligible. All patients must have tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR.\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, and histopathology consistent with diffuse WHO Grade 2-4 glioma.\n   * All other HGG must be WHO Grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Primary spinal tumor: Patients with a primary spinal HGG are eligible.\n   * Patient must not have metastatic disease.\n2. Inclusion criteria for assignment to TarGeT-D, for all strata:\n\n2.1 Presence of at Least One Relevant Actionable Somatic Mutation in IDH1 Gene, Detailed Here:\n\n* R132H, R132C, R132S, R132G or R132L.\n* Patients whose tumors harbor other alterations in addition to IDH1 mutation will potentially be eligible following consensus recommendation by the international multidisciplinary molecular screening committee.\n* Patients with IDH2 mutations are not eligible.\n* Patients with oligodendroglioma, IDH-mutant and 1p\u002F19q-codeleted are not eligible.\n\n2.2 Weight: Patients must weigh ≥35 Kg (77 lbs) at the time of enrollment on TarGeT-D.\n\n2.3 Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.4 Prior Therapy 2.4.1 Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide administered concurrently with radiotherapy is permissible. Prior administration of bevacizumab is allowed, given at least 42-day washout period is completed prior to beginning treatment on TarGeT-D. No other prior anticancer therapy for HGG will be allowed.\n\n2.4.2 Radiation therapy requirements: RT, delivered via photon or proton beam, must have been administered at a standard dose including 54 Gy in 30 fractions for DIPG, 55-59.4 Gy in 30-33 fractions for other HGG or 45-54 Gy for primary spinal cord HGG. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.\n\n2.4.3 Timing between diagnosis and start of RT: Patients must have started RT \\\u003C 42 calendar days of initial diagnosis defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n\n* Patients in pre-maintenance phase must enroll and start treatment no later than 21 calendar days post-completion of RT.\n* Patients not in pre-maintenance phase must enroll and start treatment no later than 35 calendar days post-completion of RT.\n\n2.5 Organ Function Requirements 2.5.1 Adequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3.\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Hemoglobin \\> 8 g\u002FdL (may be transfused). 2.5.2 Adequate Renal Function Defined as\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on age\u002Fgender as follows: 10 to \\\u003C 13 yrs=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 yrs=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.5.3 Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 × institutional ULN.\n* AST(SGOT)\u002FALT(SGPT) \\\u003C 3 × institutional ULN.\n* Alkaline Phosphatase \\\u003C 3 × institutional ULN. 2.5.4 Adequate Neurologic Function Defined as:\n\n  * Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not a strong inducer or inhibitor of CYP3A4\u002F5.\n  * Patients must be able to swallow oral medications to be eligible for study enrollment.\n\n2.6. Informed consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n\nExclusion Criteria:\n\n1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown potential risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy.\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD).\n   * Intra uterine hormone releasing system.\n   * Bilateral tubal occlusion.\n   * Vasectomized partner.\n   * Sexual abstinence (avoiding heterosexual intercourse).\n   * The following contraceptive measures are NOT considered effective:\n\n     * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation.\n     * Male or female condom with or without spermicide.\n     * Cap, diaphragm, or sponge with spermicide.\n2. Using the following types of concomitant medications:\n\n   * Corticosteroids: Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.\n   * Anti-cancer Agents: Concurrent anti-cancer agents are not allowed with the exception of temozolomide given concurrently with RT and as protocol-instructed post RT maintenance therapy after enrollment on TarGeT-D.\n   * Anticonvulsants: Patients who are receiving enzyme inducing anticonvulsants that are strong inducers of CYP3A4\u002F5 are not eligible.\n   * Strong CYP3A4\u002F5 inducers: Patients who are receiving strong inducers of CYP3A4\u002F5 are not eligible. Strong inducers of CYP3A4\u002F5 should be avoided from 14 days prior to or 5 half-lives (whichever is longer) enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible\n   * Selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft) should be used with caution but are not contraindicated.\n3. Other Criteria\n\n   * Infection: Patients who have an uncontrolled infection are not eligible.\n   * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n   * Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n   * Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history.\n   * Patients with prior or ongoing clinically significant illness, medical or psychiatric condition, that, in the investigator's opinion, could affect the safety of the participant, or could impair the assessment of study results are not eligible.\n   * Patients with any prior solid organ transplant are not eligible.\n   * Patients with secondary\u002Fradiation-related HGG are not eligible.\n   * Patients with metastatic\u002Fdisseminated HGG who have received CSI are not eligible.","12 Years",{"count":56,"type":22},60,[25],"The goal of this study is to determine the efficacy of the study drug olutasidenib to treat newly diagnosed pediatric and young adult patients with a high-grade glioma (HGG) harboring an IDH1 mutation.\n\nThe main question the study aims to answer is whether the combination of olutasidenib and temozolomide (TMZ) can prolong the life of patients diagnosed with an IDH-mutant HGG.",[60,61,62,63,28,33,64,65,29,66,67,68,69,70,71,72,73,74,75],"High Grade Glioma","Astrocytoma","Astrocytoma, Grade III","Astrocytoma, Grade IV","WHO Grade IV Glioma","Metastatic Brain Tumor","Thalamus Tumor","Spinal Tumor","IDH1 Mutation","IDH1 R132","IDH1 R132C","IDH1 R132H","IDH1 R132S","IDH1 R132G","IDH1 R132L","Oligodendroglioma","2026-06-10",{"date":78,"type":38},"2026-06-12",{"date":80,"type":38},"2025-02-01",{"date":82,"type":22},"2035-06",{"name":84,"class":85},"Rigel Pharmaceuticals","INDUSTRY",20,{"id":88,"slug":89,"hasResults":11,"nctId":90,"briefTitle":91,"officialTitle":92,"acronym":4,"eligibilityCriteria":93,"healthyVolunteers":11,"sex":17,"minAge":94,"maxAge":19,"enrollmentInfo":95,"targetDuration":4,"studyType":97,"phases":4,"briefSummary":98,"conditions":99,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":105,"completionDateStruct":107,"leadSponsor":109,"locationsCount":111},"100503755","targeted-pediatric-high-grade-glioma-therapy-100503755","NCT05839379","Targeted Pediatric High-Grade Glioma Therapy","Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n1. Age: Patients must be ≥12 months and ≤39 years of age at the time of enrollment onto this screening protocol.\n2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. Diagnosis must have histologic confirmation from biopsy or resection. The diagnosis of HGG must have been confirmed by pathology review at the local site. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4.\n3. Disease Status: There are no disease status requirements for enrollment.\n\n   * Measurable disease is not required. Patients without measurable disease are eligible.\n   * Patients with metastatic\u002Fdisseminated or multifocal disease or gliomatosis cerebri are eligible.\n   * Patients with a primary spinal tumor are eligible.\n   * Patients with secondary, radiation related HGG are eligible.\n4. Prior Therapy for HGG: Surgery, radiation, and\u002For dexamethasone are permissible. Temozolomide concurrent with radiation is permissible. Prior administration of avastin\u002Fbevacizumab is allowed (individual treatment arms have different washout period requirements, check individual arm eligibility). No other prior anticancer therapy for HGG will be allowed.\n\n   * Participants screening for assignment to TarGeT-L may not have received radiation.\n\n   Timing from surgery to start of RT: For patients who have started RT, radiation must have started \\\u003C42 days from definitive surgery or biopsy, however it is strongly recommended patients start RT within 31 days from definitive surgery (if patient had two surgeries, radiation must have started within 31 days from second surgery).\n5. Tumor Sample Availability OR results from previous molecular profiling\u002Ftargeted sequencing\n\n   * If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood, saliva, or buccal swab) must be submitted for comprehensive molecular screening at the time of screening enrollment.\n   * If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review.\n6. Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT (if relevant)\n\n   * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT (if completing RT).\n   * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT (if completing RT).\n   * Participants screening for TarGeT-L (lorlatinib) are eligible to enroll on TarGeT-SCR anytime between diagnosis and 31 days post definitive surgery (to allow time for molecular review).\n\nHowever, it is important to note the following:\n\n* For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT.\n* For treatment protocols that only include maintenance\u002Fadjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT\n\n  #SCREENING OPTIONS\n* OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories\n* OPTION2: Molecular screening through a national comprehensive tumor profiling program\n* OPTION3: Clinically validated targeted sequencing or focused profiling\n\nExclusion Criteria:\n\n-Tumors that do not meet HGG and DIPG diagnoses specified above","12 Months",{"count":96,"type":22},350,"OBSERVATIONAL","The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor.",[60,28,100,101,102,29,65,33,64],"Anaplastic Astrocytoma","Glioblastoma","Glioblastoma Multiforme","2026-06-08",{"date":76,"type":38},{"date":106,"type":38},"2024-08-02",{"date":108,"type":22},"2034-08-28",{"name":110,"class":45},"Nationwide Children's Hospital",21,{"id":113,"slug":114,"hasResults":11,"nctId":115,"briefTitle":116,"officialTitle":117,"acronym":4,"eligibilityCriteria":118,"healthyVolunteers":11,"sex":17,"minAge":94,"maxAge":19,"enrollmentInfo":119,"targetDuration":4,"studyType":23,"phases":121,"briefSummary":122,"conditions":123,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":125,"lastUpdatePostDateStruct":126,"startDateStruct":128,"completionDateStruct":130,"leadSponsor":131,"locationsCount":86},"100504051","phase-2-study-of-ribociclib-and-everolimus-in-hgg-and-dipg-or-ribociclib-and-temozolomide-in-dhg-h3g34-mutant-100504051","NCT05843253","Study of Ribociclib and Everolimus in HGG and DIPG or Ribociclib and Temozolomide in DHG, H3G34-mutant","Phase 2 Study of Ribociclib-Containing Post-Radiotherapy Combinations in Pediatric and Young Adult Patients Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma: Ribociclib and Everolimus for HGG\u002FDIPG Which Harbor Alterations of the Cell Cycle and\u002For PI3K\u002FmTOR Pathways AND Ribociclib and Temozolomide for DHG, H3G34-mutant","TarGeT-A study strata definitions Part1: Initial Feasibility Study for the combination of ribociclib PfOS formulation with everolimus: Enrollment on this cohort will be limited to patients aged \\\u003C21 years with primary intracranial localized HGG and DIPG\n\nPart 2\n\n* Stratum A: Patients with localized, intracranial, non-pontine, and non-thalamic HGG (who do not meet criteria for strata C-D)\n* Stratum B: Patients with DIPG\n* Stratum C: Patients with primary thalamic, spinal cord, and\u002For secondary\u002Fradiation-related HGG.\n* Stratum D: Patients with metastatic\u002Fdisseminated HGG, multifocal HGG, and\u002For gliomatosis cerebri who received CSI.\n\nStratum E\n\n* Stratum E: Patients with localized DHG, H3G34-mutant.\n\nInclusion Criteria:\n\n1. Inclusion criteria already met to enroll on TarGeT-SCR (central molecular and histopathologic screening) based on:\n\n   1.1) Age: patients must be ≥12 months and ≤39 years of age at the time of enrollment on TarGeT-SCR. For the Part 1 Initial Feasibility Cohort (receiving ribociclib and everolimus) only: patients must be \\\u003C21 years of age at the time of enrollment on this protocol.\n\n   1.2) Diagnosis: patients with newly-diagnosed HGG, including DIPG are eligible. All patients must have histologic confirmation tumor tissue from diagnostic biopsy or resection, without exceptions. The diagnosis of HGG, including DIPG, must have been confirmed through TarGeT-SCR:\n   * For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2\u002F3 of the pons, with histopathology, consistent with diffuse WHO grade 2-4 glioma\n   * All other HGGs must be WHO grade 3 or 4.\n\n   1.3) Disease status: There are no disease status requirements for enrollment\n   * Patients without measurable disease are eligible.\n   * Patients with metastatic or multifocal disease or gliomatosis cerebri who received upfront CSI are eligible\n   * Patients with a primary spinal HGG are eligible\n   * Patients with secondary, radiation-related HGG are eligible.\n2. Inclusion criteria for assignment to TarGeT-A, for all strata:\n\n2.1) Presence of at least one relevant actionable somatic alteration, detailed here:\n\n* Pathogenic alterations presumed to cause activation of cell cycle:\n* Amplification of CDK4 or CDK6\n* Deletion of CDKN2A, CDKN2B, or CDKN2C\n* Amplification of CCND1 or CCND2\n* Pathogenic alterations presumed to cause activation of the PI3K\u002FmTOR pathway:\n* Deletion or mutation of PTEN\n* Mutation or amplification of PIK3CA\n* Mutation of PIK3R1\n* Deletion or mutation of TSC1 or TSC2\n* Patients with evidence of homozygous (biallelic) RB1 loss by sequencing are excluded from TarGeT-A\n* Patients whose tumors harbor other alterations suspected to activate the cell cycle and\u002For PI3K\u002FmTOR pathway could potentially also be eligible, but only following consensus recommendation by the international multidisciplinary molecular screening committee.\n* For Stratum E: H3G34 (R\u002FV) mutation\n\n2.2) Performance Level: Karnofsky ≥ 50% for patients \\> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of ag. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n\n2.3) Prior Therapy for HGG:\n\n* Surgery, RT, dexamethasone are permissible. Temozolomide administered concurrently with RT is permissible. Avastin\u002Fbevacizumab use is permitted given the last dose was administered \\> 21 days prior to enrollment. No other prior anticancer therapy for HGG will be allowed.\n* Patients must have received photon or proton RT.\n* Patients must have started RT \\\u003C 42 calendar days from initial diagnosis defined as the date of diagnostic biopsy or resection. If a patient underwent 2 upfront surgeries (e.g., biopsy then resection or debulking), this is the date of the second surgery.\n* RT delivered via photon or proton beam, must have been administered at a standard dose including (54 Gy in 30 fractions for DIPG, 54-59.4 Gy in 30-33 fractions), 45 Gy-54 Gy for primary spinal disease, and\u002For 36 Gy-39.6 Gy craniospinal for patients with spinal or leptomeningeal metastatic disease with supplemental boost to 45-54 Gy for metastasis within the thecal sac and 54 Gy-60 Gy for intracranial metastasis. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Sponsor-Investigator to confirm eligibility prior to study enrollment.\n* Patients must enroll and start treatment No later than 35 calendar days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT.\n\n2.4) Organ Function Requirements\n\n2.4.1) Adequate Bone Marrow Function Defined as:\n\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm3\n* Platelet count ≥ 100,000\u002Fmm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)\n* Hemoglobin \\>8 g\u002FdL (may be transfused)\n\n2.4.2) Adequate Renal Function Defined as:\n\n* Creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2 OR\n* Maximum serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age\u002Fgender as follows: 1 to \\\u003C 2 years=0.6 mg\u002FdL for males and females; 2 to \\\u003C 6 years=0.8 mg\u002FdL for males and females; 6 to \\\u003C 10 years= 1.0 mg\u002FdL for males and females; 10 to \\\u003C 13 years=1.2 mg\u002FdL for males and females. 13 to \\\u003C 16 years=1.5 mg\u002FdL for males and 1.4 mg\u002FdL for females.\n\n2.4.3) Adequate Liver Function Defined as:\n\n* Total bilirubin must be ≤ 1.5 times institutional upper limit of normal for age\n* AST(SGOT)\u002FALT(SGPT) ≤ 3 times institutional upper limit of normal\n* Serum albumin ≥ 2g\u002FdL\n\n2.4.4) Adequate Cardiac Function Defined as:\n\n* Ejection fraction of ≥ 50% by echocardiogram\n* QTc ≤ 450 msec (by Bazett formula)\n\n2.4.5) Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if well-controlled on anticonvulsants that are not strong inducers or inhibitors of CYP3A4\u002F5.\n\n2.4.6) Adequate Pulmonary Function Defined as: No evidence of dyspnea at rest, and a pulse oximetry \\>94% on room air if there is clinical indication for determination.\n\n2.5) Ability to take medications by mouth: For ribociclib and everolimus strata, patients must be able to take study medications by mouth as administration via NG\u002FNJ\u002FG tube is not allowed.\n\n2.6) Informed Consent: All patients and\u002For their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines\n\n2.7) Contraception: Male and female patients of childbearing potential must be willing to use a highly effective contraception method.\n\nExclusion Criteria\n\n1. Pregnant or Breast-Feeding Pregnant or breast-feeding women will not be entered on this study due to known potential risks of fetal and teratogenic adverse events as seen in animal\u002Fhuman studies. Pregnancy tests must be obtained in girls who are post-menarchal. Patients of childbearing or child fathering potential must agree to use at least one highly effective method of contraception while being treated on this study and for 3 months after completing therapy. A woman is considered of childbearing potential if she is fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Male participants should refrain from sperm donation throughout the duration of treatment and for 3 months after completion of therapy\n\n   A highly effective contraception method is defined as one that results in a low failure rate (\\\u003C1% per year) when used consistently and correctly. The following are considered highly effective contraception methods:\n   * Combined estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation.\n   * Progesterone-only hormonal contraception associated with inhibition of ovulation.\n   * Intra Uterine Device (IUD)\n   * Intra Uterine hormone releasing system\n   * Bilateral tubal occlusion\n   * Vasectomized partner\n   * Sexual abstinence (avoiding having heterosexual intercourse) The following contraceptive measures are NOT considered effective\n   * Progesterone-only hormonal contraception (birth control pill) that that does NOT stop ovulation\n   * Male or female condom with or without spermicide\n   * Cap, diaphragm or sponge with spermicide\n2. Concomitant Medications\n\n   * Patients receiving corticosteroids are eligible. The use of corticosteroids must be reported.\n   * Patients who are currently receiving another investigational drug are not eligible.\n   * Patients who are currently receiving other anti-cancer agents are not eligible, with the exception of temozolomide given concurrently with RT only.\n   * Patients who are receiving enzyme inducing anticonvulsants that are strong inducers or inhibitors of CYP3A4\u002F5 are not eligible.\n   * Patients who are receiving strong inducers or inhibitors of CYP3A4\u002F5 are not eligible and should be avoided from 14 days prior to enrollment to the end of the study.\n   * Patients who are receiving medications known to prolong QTc interval are not eligible.\n   * Patients who are receiving therapeutic anticoagulation with warfarin or other coumadin-derived anticoagulants are not eligible. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed as long as the patient has adequate coagulation defined as aPTT \\\u003C 1.5Xs ULN and INR \\\u003C 1.5.\n3. Patients who have an uncontrolled infection are not eligible.\n4. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.\n5. Patients with known clinically significant active malabsorption syndrome or other condition that could affect absorption are not eligible.\n6. Patients with prior or ongoing clinically significant medical or psychiatric condition that, in the investigator's opinion, could affect the safety of the subject, or could impair the assessment of study results are not eligible.",{"count":120,"type":22},120,[25],"The goal of this study is to determine the efficacy of the 1) ribociclib and everolimus to treat pediatric and young adult patients newly diagnosed with a high-grade glioma (HGG), including DIPG, that have genetic changes in pathways (cell cycle, PI3K\u002FmTOR) that these drugs target or 2) ribociclib and temozolomide to treat pediatric and young adult patients newly diagnosed with diffuse hemispheric glioma (DHG), H3G34-mutant.\n\nThe main question the study aims to answer is whether the combinations of ribociclib and everolimus or ribociclib and temozolomide can prolong the life of patients diagnosed with HGG\u002FDIPG or DHG H3G34-mutant.",[60,28,100,101,102,29,65,33,64,124],"Diffuse Hemispheric Glioma, H3 G34-Mutant","2026-05-27",{"date":127,"type":38},"2026-05-29",{"date":129,"type":38},"2024-08-22",{"date":108,"type":22},{"name":110,"class":45},{"id":133,"slug":134,"hasResults":11,"nctId":135,"briefTitle":136,"officialTitle":137,"acronym":4,"eligibilityCriteria":138,"healthyVolunteers":11,"sex":17,"minAge":139,"maxAge":140,"enrollmentInfo":141,"targetDuration":4,"studyType":23,"phases":143,"briefSummary":144,"conditions":145,"keywords":146,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":147,"lastUpdatePostDateStruct":148,"startDateStruct":150,"completionDateStruct":152,"leadSponsor":154,"locationsCount":156},"100639343","phase-2-a-study-of-vrt106-in-combination-with-radiotherapy-in-adult-patients-with-diffuse-midline-glioma--diffuse-intrinsic-pontine-glioma-100639343","NCT07589257","A Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma \u002F Diffuse Intrinsic Pontine Glioma","A Single-Arm, Open-Label, Multicenter Phase II Clinical Study of VRT106 in Combination With Radiotherapy in Adult Patients With Diffuse Midline Glioma \u002F Including Diffuse Intrinsic Pontine Glioma","Inclusion Criteria:\n\n* Voluntary signing of the Informed Consent Form (ICF), indicating understanding of the study and willingness and ability to comply with all study procedures.\n* Male or female adults aged 18 to 75 years at the time of signing the ICF.\n* Histologically or cytologically confirmed H3 K27-altered diffuse midline glioma (DMG), or a diagnosis of DIPG based on brain contrast-enhanced MRI: tumor originating in the pons, occupying \\>50% of the pons volume, with diffuse brainstem enlargement.\n* Karnofsky Performance Status (KPS) score ≥ 60.\n* Expected survival time ≥ 3 months.\n\nExclusion Criteria:\n\n* Individuals with extracranial metastases.\n* Presence of spinal cord tumors or evidence of leptomeningeal disease dissemination.\n* Active hemorrhage detected on cranial MRI scan prior to enrollment.\n* Inability to undergo cranial MRI scanning (e.g., due to contraindications or incompatible implants).\n* Prior receipt of oncolytic virus therapy or other gene therapy agents.","18 Years","75 Years",{"count":142,"type":22},10,[25],"To Evaluate the Preliminary Efficacy and Safety\u002FTolerability of VRT106 Combined with Radiotherapy in Adult Patients with DMG\u002FDIPG",[29,28],[29,28],"2026-05-13",{"date":149,"type":38},"2026-05-15",{"date":151,"type":22},"2026-05-07",{"date":153,"type":22},"2028-12-31",{"name":155,"class":85},"Guangzhou Virotech Pharmaceutical Co., Ltd.",1,{"id":158,"slug":159,"hasResults":11,"nctId":160,"briefTitle":161,"officialTitle":162,"acronym":4,"eligibilityCriteria":163,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":164,"enrollmentInfo":165,"targetDuration":4,"studyType":23,"phases":167,"briefSummary":169,"conditions":170,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":175,"lastUpdatePostDateStruct":176,"startDateStruct":178,"completionDateStruct":180,"leadSponsor":182,"locationsCount":156},"100503471","phase-1-loc3car-locoregional-delivery-of-b7-h3-car-t-cells-for-pediatric-patients-with-primary-cns-tumors-100503471","NCT05835687","Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors","Loc3CAR: Locoregional Delivery of B7-H3-specific Chimeric Antigen Receptor Autologous T Cells for Pediatric Patients With Primary CNS Tumors","Inclusion Criteria: Screening Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor\n3. For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor\n4. For Cohort B, must meet one of the following criteria:\n\n   * Adequate tumor tissue from primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \\[IHC\\] or H3K27M mutation if pontine lesion)\n   * Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)\n   * Has presumptive\u002Fsuspected brainstem high-grade neoplasm with available imaging for central imaging review\n5. Life expectancy of \\> 12 weeks\n6. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Screening Eligibility All Participants\n\n1\\. Participant has other clinically significant medical disorders (e.g. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that could compromise their ability to tolerate protocol therapy or would interfere with study procedure.\n\nInclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Age ≤ 21 years of age\n2. Primary CNS tumor with measurable or evaluable disease and meets criteria for either Cohort A or B:\n\n   * Cohort A: relapsed\u002Frefractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive\n   * Cohort B: Diffuse midline glioma AND tumor is:\n\n     * B7-H3 positive if non-pontine\n     * OR H3K27-altered diffuse midline pontine glioma\n     * OR radiographically-confirmed classic\u002Ftypical DIPG\n3. Estimated life expectancy of \\>12 weeks\n4. Karnofsky or Lansky performance score ≥50\n5. Participant of childbearing\u002Fchild-fathering potential agrees to use contraception\n6. For females of childbearing age:\n\n   * Not pregnant with negative serum pregnancy test\n   * Not lactating with intent to breastfeed\n7. Chemotherapy\u002Fbiologic therapy must be discontinued ≥ 7 days prior to enrollment\n8. The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment\n9. At least 30 days from most recent cell infusion prior to enrollment.\n10. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday\n11. Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program\n12. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Procurement and T-cell Production Eligibility\n\n1. Known primary immunodeficiency or acquired immunodeficiency.\n2. Known HIV positivity\n3. Severe intercurrent bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection).\n4. Rapidly progressive disease\n5. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments.\n6. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study.\n\nInclusion Criteria: Treatment Eligibility\n\nCohort A\n\n* Relapsed\u002Frefractory non-brainstem CNS primary tumor\n* Tumor must be considered B7-H3 positive\n\nCohort B\n\n* Diffuse Midline Glioma - Must meet one of the following criteria\n\n  * Tumor is considered B7-H3 positive\n  * H3K27-altered diffuse midline pontine glioma\n  * Radiographically-confirmed classic\u002Ftypical DIPG\n* Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy\n\nAll participants\n\n1. Age ≤ 21 years old\n2. Primary CNS tumor with measurable or evaluable disease\n3. Available autologous T-cell product that has met GMP release criteria\n4. Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt\n5. First CAR T cell infusion is planned\u002Fscheduled ≥ 5 days from CNS surgery, including catheter placement\n6. The following treatments must be discontinued for the specified duration prior to treatment enrollment:\n\n   * Radiation therapy: ≥ 6 weeks\n   * Bevacizumab: ≥ 28 days\n   * Cytotoxic chemotherapy: ≥ 21 days\n   * Biologic agents: ≥ 7 days\n   * Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Cellular therapy: ≥ 30 days\n   * Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter)\n   * Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg\u002Fm\\^2\u002Fday. Corticosteroid physiologic replacement therapy for management of pituitary\u002Fadrenal axis insufficiency and\u002For topical administration (e.g. inhaled or dermatologic) is allowed.\n7. Estimated life expectancy of \\>8 weeks\n8. Karnofsky or Lansky performance score ≥ 50\n9. Echocardiogram with a left ventricular ejection fraction ≥ 50%\n10. Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL\u002Fmin\u002F1.73m\\^2.\n11. Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.\n12. Total Bilirubin ≤3 times the upper limit of normal for age.\n13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.\n14. Hemoglobin \\>8.0 g\u002FdL (can be transfused).\n15. Platelet count \\>50,000\u002Fmm\\^3 (can be transfused).\n16. Absolute neutrophil count (ANC) ≥1000\u002FuL.\n17. Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.\n18. Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy.\n19. Male participants of child-fathering potential agree to use contraception\n20. Female participants of childbearing potential:\n\n    * Negative serum pregnancy test within 7 days prior to infusion\n    * Not lactating with intent to breastfeed\n    * If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom\n21. Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines\n\nExclusion Criteria: Treatment Eligibility-All Participants\n\n1. Participant has a non-programmable ventricular shunt that could compromise study therapy\n2. Participant has a reservoir catheter or shunt in a location that could compromise study therapy or patient safety\n3. Known primary immunodeficiency or acquired immunodeficiency.\n4. Known HIV positivity\n5. Severe intercurrent bacterial, viral or fungal infection\n6. Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry\n7. Receiving therapy as outlined above during the 'wash-out' period\n8. Rapidly progressing disease\n9. Received any live vaccines within 30 days\n10. Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments\n11. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study\n12. Evidence of uncontrolled hypertension. Anti-hypertensive medications are permitted if on a stable dose.\n13. Uncontrolled seizures","21 Years",{"count":166,"type":22},48,[168],"PHASE1","Loc3CAR is a Phase I clinical trial evaluating the use of autologous B7-H3-CAR T cells for participants ≤ 21 years old with primary CNS neoplasms. B7-H3-CAR T cells will be locoregionally administered via a CNS reservoir catheter. Study participants will be divided into two cohorts: cohort A with B7-H3-positive relapsed\u002Frefractory non-brainstem primary CNS tumors, and cohort B with diffuse midline gliomas (DMG). Participants will receive four (4) B7-H3-CAR T cell infusions over a 4 week period. The purpose of this study is to find the maximum (highest) dose of B7-H3-CAR T cells that are safe to give patients with primary brain tumors.\n\nPrimary objectives\n\n* To determine the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the locoregional delivery of autologous B7-H3-CAR T cells in patients ≤ 21 years of age with recurrent\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n\nSecondary objectives\n\n* To assess the efficacy, defined as sustained objective response, a partial response (PR) or complete response (CR) observed anytime on active treatment with B7-H3-CAR T cells in patients with relapsed\u002Frefractory B7-H3+ primary CNS tumors (Cohort A) or DMG (Cohort B).\n* To characterize and monitor neurologic toxicities in patients while on study (Cohort A and B).",[171,172,29,173,60,101,174],"Central Nervous System Neoplasms","Atypical Teratoid\u002FRhabdoid Tumor","Ependymoma","Medulloblastoma","2026-05-01",{"date":177,"type":38},"2026-05-05",{"date":179,"type":38},"2023-04-27",{"date":181,"type":22},"2028-03",{"name":183,"class":45},"St. Jude Children's Research Hospital",{"id":185,"slug":186,"hasResults":11,"nctId":187,"briefTitle":188,"officialTitle":189,"acronym":4,"eligibilityCriteria":190,"healthyVolunteers":11,"sex":17,"minAge":94,"maxAge":139,"enrollmentInfo":191,"targetDuration":4,"studyType":23,"phases":193,"briefSummary":194,"conditions":195,"keywords":196,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":208,"lastUpdatePostDateStruct":209,"startDateStruct":211,"completionDateStruct":213,"leadSponsor":215,"locationsCount":217},"100434949","phase-1-rhsc-dipgvax-plus-checkpoint-blockade-for-the-treatment-of-newly-diagnosed-dipg-and-dmg-100434949","NCT04943848","rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG","A Phase I Clinical Trial of Neo-antigen Heat Shock Protein Vaccine (rHSC-DIPGVax) in Combination With Checkpoint Blockade for the Treatment of Diffuse Intrinsic Pontine Glioma (DIPG) and Diffuse Midline Glioma in Childhood","Inclusion Criteria:\n\n* Subjects with newly diagnosed typical or non-typical, biopsy-proven DIPG or DMG are eligible for study enrollment. Biopsy is not required for subjects with radiographically typical DIPG meeting imaging criteria. Biopsy is required for DMG's and non-radiographically typical DIPG. Histone mutation must be confirmed by pathology report. Radiographically typical DIPG defined as a tumor with a pontine epicenter and diffuse involvement of more than 2\u002F3 of the pons.\n\n  = Subjects ages \\> or = to 12 months and \\\u003C or = 18 years (\"Lead In\", Part A, and Part B require first three patients be \\> or = to 12 years of age)\n* BSA \\> or = 0.35m2 at the time of study enrollment\n* Performance score: Karnofsky \\>50% of subjects \\>16 years of age and Lansky \\> or = 50 for subjects \\\u003C or = 16 years of age. Subjects who are unable to walk because of paralysis but are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n* Must start radiation therapy within 42 days from date of diagnostic imaging. C1D1 must be within 42 days to 70 days post radiation (6-10 weeks). Patients CANNOT receive temozolomide during radiation\n* Corticosteroids should be weaned as tolerated after radiation therapy with the goal of \\\u003C or = 0.5mg\u002Fkg\u002Fday for a minimum of 7 days prior to enrollment.\n* Subjects must have measurable disease\n\nExclusion Criteria:\n\n* Patients cannot receive temozolomide during radiation\n* Disseminated disease\n* Subjects who have received any cancer therapy except for radiation\n* Autoimmune or immune disorders\n* Active respiratory disorder or infection\n* Active viral infection",{"count":192,"type":22},36,[168],"This is a phase I, open label, plus expansion clinical trial evaluating the safety and tolerability of rHSC-DIPGVax in combination with BALSTILIMAB and ZALIFRELIMAB. rHSC-DIPGVax is an off-the-shelf neo-antigen heat shock protein containing 16 peptides reflecting neo-epitopes found in the majority of DIPG and DMG tumors. Newly diagnosed patients with DIPG and DMG who have completed radiation six to ten weeks prior to enrollment are eligible.",[28,29],[197,198,199,200,201,202,203,204,205,206,207],"Immunotherapy","Cancer vaccine","Checkpoint blockade","DIPG","Diffuse intrinsic pontine glioma","High grade glioma","DMG","Diffuse midline glioma","rHSC-DIPGVax","Balstilimab","Zalifrelimab","2026-03-16",{"date":210,"type":38},"2026-03-17",{"date":212,"type":38},"2022-01-10",{"date":214,"type":22},"2027-09",{"name":216,"class":45},"Ann & Robert H Lurie Children's Hospital of Chicago",3,{"id":219,"slug":220,"hasResults":11,"nctId":221,"briefTitle":222,"officialTitle":223,"acronym":224,"eligibilityCriteria":225,"healthyVolunteers":11,"sex":17,"minAge":226,"maxAge":4,"enrollmentInfo":227,"targetDuration":4,"studyType":23,"phases":229,"briefSummary":231,"conditions":232,"keywords":234,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":239,"lastUpdatePostDateStruct":240,"startDateStruct":242,"completionDateStruct":244,"leadSponsor":246,"locationsCount":248},"100475900","phase-3-biological-medicine-for-diffuse-intrinsic-pontine-glioma-dipg-eradication-20-100475900","NCT05476939","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication 2.0","Biological Medicine for Diffuse Intrinsic Pontine Glioma (DIPG) Eradication","BIOMEDE 2","Eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Diagnosis Criteria:\n\n  * Diagnosis of DIPG (clinical and radiological). As biopsy is not standard for these tumors, an informed consent is required for the necessary histological verification. \\[Biopsy-part of BIOMEDE 2.0 trial\\]. OR\n  * Histological diagnosis of DIPG (i.e. H3K28M or EZHIP positive Diffuse Midline Glioma located in the pons) in case the tumor biopsy was performed before study entry. The diagnosis will be defined by 1\u002F diffuse glioma, 2\u002F H3K28M mutation or loss of H3K28 trimethylation together with EZHIP overexpression. In this situation, patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Molecular diagnosis of DIPG (i.e. H3K28M) in case a liquid biopsy (CSF or blood) was performed before study entry, in a patient who could not undergo a tumor biopsy because it was too dangerous according to the patient's clinical condition. The diagnosis will be defined by 1\u002F DIPG, 2\u002F H3K28M mutation. In this situation, patient will sign the consent after the diagnosis to allow collection of the molecular report. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG), H3K28M mutant or with H3K28 trimethylation loss together with EZHIP overexpression, will be eligible for the trial after biopsy or surgery. As biopsy and surgery is considered as standard practice for these locations, informed consent for the biopsy will not be necessary. Patient will sign the consent after the diagnosis to allow central review and biomarkers assessment thereafter. OR\n  * Non-DIPG diffuse midline gliomas (ND-DMG) will be eligible for the trial before the biopsy in case the diagnosis is clinically or radiologically suspected. Informed consent for the biopsy and molecular analysis will be necessary. Then, if the central pathology review concludes to a ND-DMG with H3K28M mutant or H3K28 trimethylation loss together with EZHIP overexpression, these patients will be eligible for the treatment part of the trial.\n* Eligible for a biopsy, or biopsy material available for the biomarker assessment.\n* Age \\> 6 months, with no upper age limit. Children between 6 months and 3 years will be discussed on a case by case basis for inclusion in the study for the feasibility of the stereotactic biopsy.\n* Eligible for cerebral or craniospinal radiotherapy.\n* Tumor at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy even for another neoplasm. Surgery is allowed when performed for diagnostic or therapeutic purpose.\n* Metastatic diseases or spinal tumors allowed; in this case, patients would receive craniospinal or spinal radiotherapy and medical treatment (everolimus or ONC201) will be postponed and only started after the end of radiotherapy.\n* Patients must be affiliated to a social security system or beneficiary of the same according to local requirements.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study-specific procedures are conducted according to local, regional or national guidelines.\n\nNon eligibility criteria for the inclusion (registration) in BIOMEDE 2.0 study:\n\n* Uncontrolled spontaneous massive intratumor bleeding. Patients with post-operative bleeding will be allowed to enter the study provided the hemorrhage is controled. Same rule applies for the other post-operative complications (infection, CSF leakage, absence of wound closure, subdural collection…).\n* Any other concomitant anti-cancer treatment not foreseen by this protocol is not allowed, except corticosteroids and Bevacizumab which are allowed during the protocol. Bevacizumab is not allowed before and until 15 days after the surgery. The use of bevacizumab and corticosteroids will be taken into account when judging the possibility of progression\u002Fpseudoprogression.\n* Any other cancer diagnosed during the last 5 years.\n* Uncontrolled intercurrent illness or active infection.\n* Any other co-morbid condition that in the investigator's opinion would impair study participation.\n* Unable for medical follow-up (geographic, social or mental reasons).\n* Patient previously treated with irradiation on the brainstem for another neoplasm.\n* Participation in another clinical study with an investigational product while on study treatment.\n* Patient under guardianship or deprived of his\u002Fher liberty by a judicial or administrative decision or incapable of giving his\u002Fher consent.\n\nEligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Patient enrolled in the BIOMEDE 2.0 study.\n* Life expectancy \\> 12 weeks after the start of study treatment.\n* Histological diagnosis of DIPG (as per the WHO criteria) confirmed by central pathology review, OR Typical radiology of a DIPG (mandatory central radiological review) as well as the short clinical history (less than three months of pre-existing symptoms) in case of suspected DIPG but no histological confirmation (tumor biopsy performed but not informative), or suspected DIPG with detection of H3K28M mutation in the CSF or blood (ctDNA analysis in the CSF or blood), OR Histological diagnosis of ND-DMG confirmed by central pathology review, with mutation in the histone H3.1, H3.2, H3.3 genes, or loss of H3K28me3 and EZHIP overexpression by immunohistochemistry.\n* Karnofsky performance status scale or Lansky Play Scale \\> 50%. The PS should not take the neurologic deficit per se into account. NB: Children and adults with a worse performance status due to glioma-related motor paresis can be included.\n* Highly effective and appropriate contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment.\n* Negative pregnancy test (serum beta-HCG or urinary test) evaluated within one week prior randomization in sexually active females of reproductive potential.\n* Absolute neutrophil count \\> 1.0 x 10\\^9\u002Fl, Platelets \\> 100 x 10\\^9\u002Fl.\n* Total bilirubin \\\u003C 1.5 x ULN, AST and ALT\\\u003C 2.5 x ULN.\n* Serum creatinine \\\u003C 1.5 X ULN for age. If serum creatinine \\> 1.5 x ULN, creatinine clearance must be \\> 70 ml\u002Fmin\u002F1.73 m² (as per local practice).\n* Normal coagulation tests within the local reference ranges.\n* Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before randomization according to local, regional or national guidelines.\n\nNon Eligibility criteria for the randomization in BIOMEDE 2.0 study:\n\n* Current organ toxicity \\> grade 2 according to the NCI-CTCAE version 5.0, especially cardiovascular or renal disease (including but not limited to: congenital long QT syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment).\n* Patients with the following cardiac history cannot take ONC201:\n\n  * Prolongation of QT\u002FQTcF interval (QTc interval \\> 480 milliseconds) preferably using Frederica's QT correction formula on two ECGs separated by at least 48 hours.\n  * A history of Torsades de pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome.\n  * Required concomitant use of medication(s) known to prolong the QT\u002FQTc interval.\n\nIn this case, patients will be treated in the Everolimus arm without randomization (except if contra-indication to Everolimus).\n\n* Pregnant or breastfeeding women.\n* Patients with chronic HBV disease compatible with the trial are not excluded from the study. These patients randomized to everolimus treatment will have regular viral load monitoring throughout the study.\n* Patients taking strong P450 inhibitors or inducers or PgP inhibitors are not excluded from the study but drug concentration of everolimus should be monitored carefully to avoid toxicity. Preferably alternative medications should be considered.\n* Patient with known congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of Everolimus (active substance, other rapamycin derivatives or excipients) will not be randomized and will be treated in the ONC201 arm (except if contra-indication to ONC201).\n* Patients with known hypersensitivity to any component of ONC201 (drug product or excipients) will not be randomized and will be treated in the Everolimus arm (except if contra-indication to Everolimus).","6 Months",{"count":228,"type":22},433,[230],"PHASE3","The BIOMEDE 2.0 study is the second stage of the BIOMEDE multi-arm, multistage rolling programme (adaptive platform protocol).\n\nIt is a multicenter, randomized, open-label, controlled phase-3 trial evaluating efficacy of ONC201 in comparison with everolimus (primary objective based on internal comparison) and subsequently to historical controls.\n\nTwo treatment groups will be compared. A switch between treatment groups is allowed after confirmation of the disease progression (real-time central review blinded to the treatment arm allocation). Study treatment will be continued until centrally confirmed disease progression (either radiologically or histologically), unacceptable toxicity or consent withdrawal.\n\nThe final conclusion of the trial will be successful for ONC201, if ONC201 is found significantly superior to everolimus in terms of centrally-reviewed PFS (Progression-free survival) from randomization (internal comparison) either overall, considering ND-DMG and DIPG-patients together, or in the subgroup of ND-DMG patients alone. In other cases, Everolimus will remain the standard arm unless it appears associated with an excess of toxicity compared to ONC201 which could then be discussed as a new standard.",[28,29,233],"Diffuse Midline Glioma, H3K27-altered",[235,236,237,238],"Children","Adolescents","Adults","Newly diagnosed","2026-02-03",{"date":241,"type":38},"2026-02-05",{"date":243,"type":38},"2022-09-29",{"date":245,"type":22},"2031-09",{"name":247,"class":45},"Gustave Roussy, Cancer Campus, Grand Paris",50,{"id":250,"slug":251,"hasResults":11,"nctId":252,"briefTitle":253,"officialTitle":254,"acronym":4,"eligibilityCriteria":255,"healthyVolunteers":11,"sex":17,"minAge":256,"maxAge":19,"enrollmentInfo":257,"targetDuration":4,"studyType":23,"phases":259,"briefSummary":260,"conditions":261,"keywords":4,"overallStatus":265,"whyStopped":4,"lastUpdateSubmitDate":266,"lastUpdatePostDateStruct":267,"startDateStruct":268,"completionDateStruct":270,"leadSponsor":272,"locationsCount":156},"100622873","phase-1-combination-adi-peg-20-tmz-and-rt-for-treatment-of-newly-diagnosed-high-grade-glioma-hgg-100622873","NCT07389278","Combination ADI-PEG 20, TMZ, and RT for Treatment of Newly Diagnosed High-grade Glioma (HGG)","A Phase 1\u002F2 Study of Pegylated Arginine Deiminase (ADI-PEG 20) Plus Radiotherapy (RT) and Temozolomide (TMZ) in Children, Adolescents, and Young Adults With Newly Diagnosed High-grade Glioma (HGG)","Inclusion Criteria:\n\n1. Participants must have histologically and molecularly confirmed newly diagnosed World Health Organization (WHO) grade 3 or 4 glioma.\n\n   1. Phase 1: any newly diagnosed HGG (including DMG of any location and primary spinal cord tumors).\n   2. Phase 2:\n\n      * Cohort 1: Newly diagnosed non-pontine, non-spinal cord HGG histone-wildtype.\n      * Cohort 2: Newly diagnosed non-pontine, non-spinal cord H3K27 altered diffuse midline glioma (DMG).\n      * Cohort 3: Newly diagnosed non-pontine, non-spinal cord H3G34 mutant diffuse hemispheric glioma (DHG).\n2. Prior surgery: must have undergone maximal safe resection. For patients with DMG of the pons, biopsy is sufficient.\n3. Prior Therapy: Participants must NOT have received ANY prior therapy (except surgery) before enrollment on study.\n4. Tumor Tissue Requirement: Participants must have sufficient tumor tissue (5-10 unstained formalin-fixed paraffin-embedded (FFPE) slides or a tumor block) for study enrollment.\n5. Age:\n\n   Phase 1:\n\n   o 3 to \\\u003C18 years of age.\n\n   Phase 2:\n   * Cohort 1: 3 to 25 years of age.\n   * Cohorts 2 \\& 3: 3 to 39 years of age.\n6. Performance Score: Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants \\\u003C=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n7. Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.\n8. Organ Function Requirements:\n\n   1. Peripheral absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3.\n   2. Platelet count \\>= 100,000\u002Fmm\\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n   3. Creatinine Clearance (CrCl) or estimated glomerular filtration rate (eGFR) with cutoff value of ≥ 60 mL\u002Fmin for renal function in participants with age ≥ 18 years. For participants \\\u003C 18 years old, estimate eGFR using the Schwartz equation. eGFR (mL\u002Fmin\u002F1.73 m\\^2) = (k × Height (cm)) \u002F Serum Creatinine (mg\u002FdL).\n   4. Total bilirubin \\\u003C= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \\\u003C 3 x ULN or direct bilirubin \\\u003C 1.5 x ULN.\n   5. alanine aminotransferase (ALT) \\\u003C= 3 x ULN.\n   6. aspartate aminotransferase (AST) \\\u003C= 3 x ULN.\n   7. Participants with seizure disorder may be enrolled if well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.\n9. The effects of ADI-PEG 20 have been shown to be associated with embryofetal toxicity in rodents. For this reason and because chemotherapy used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.\n10. A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.\n11. Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution.\n\nExclusion Criteria:\n\n1. Participants who have received any systemic therapy or RT, including any investigational agents.\n2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20 such as pegylated compounds.\n3. Phase 2 cohorts: tumors with epicenter in pons or spinal cord\n4. Participants with metastatic or leptomeningeal disease. Multi-focal disease should be discussed with the study chairs,\n5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that would interfere with the study.\n6. Women of childbearing potential must not be pregnant or breast-feeding.\n7. Human immunodeficiency virus (HIV)-positive participants will be ineligible if HIV therapy regimen has not been stable for at least 4 weeks or there is intent to change the regimen within 8 weeks following enrollment, or if they are severely immunocompromised.\n8. Corrected QT Interval (QTc) cutoff \\>480 ms.\n\nImportant note: The eligibility criteria listed above are interpreted literally and cannot be waived.","3 Years",{"count":258,"type":22},97,[168,25],"This is an open label, intra-patient dose escalation, to evaluate ADI-PEG 20, in combination with Temozolomide (TMZ) and radiation therapy (RT) in children, adolescents and young adult patients with newly diagnosed high grade glioma (HGG).",[101,262,263,29,264],"High-Grade Glioma (WHO III-IV)","High-grade Glioma","Diffuse Hemispheric Glioma, H3G34 Mutant","NOT_YET_RECRUITING","2026-01-28",{"date":241,"type":38},{"date":269,"type":22},"2026-03-09",{"date":271,"type":22},"2035-06-30",{"name":273,"class":45},"Sabine Mueller, MD, PhD",{"id":275,"slug":276,"hasResults":11,"nctId":277,"briefTitle":278,"officialTitle":279,"acronym":4,"eligibilityCriteria":280,"healthyVolunteers":11,"sex":17,"minAge":281,"maxAge":164,"enrollmentInfo":282,"targetDuration":4,"studyType":23,"phases":283,"briefSummary":284,"conditions":285,"keywords":286,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":298,"lastUpdatePostDateStruct":299,"startDateStruct":300,"completionDateStruct":302,"leadSponsor":304,"locationsCount":156},"100497836","phase-1-fus-etoposide-for-dmg-100497836","NCT05762419","FUS Etoposide for DMG","A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)","Inclusion Criteria:\n\n* Ages 4 - 21 years\n* Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami, and\u002For histological confirmation of H3K27M mutation of pontine or thalamic glioma. Subjects must have evidence of clinical and\u002For radiographic progression of disease.\n* Lansky performance status score of at least 60 for subjects 16 years of age or younger.\n* Karnofsky performance status of at least 60 for subjects greater than 16 years of age\n* Organ Function:\n\n  * Adequate hematologic function defined as:\n\n    * Peripheral absolute neutrophil count ≥ 1,500\u002FµL\n    * Platelet count ≥ 100,000\u002FµL\n    * Partial thromboplastin time (PTT) and activated partial thromboplastin time (APTT): within normal institutional limits\n  * Adequate renal function defined as:\n\n    * Potassium and magnesium levels within institutional limits\n    * Serum creatinine below the institutional upper limit of normal (ULN) for age and gender, or creatinine clearance: ≥ 60 mL\u002Fmin\u002F1.73m2\n  * Adequate hepatic function defined as:\n\n    * Total bilirubin below the institutional ULN for age\n    * Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 2.5 × institutional ULN\n* Prior Therapy:\n\n  * Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.\n  * Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: at least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy.\n  * Anti-cancer agents not known to be myelosuppressive: at least 7 days must have elapsed from last dose of agent.\n  * Antibodies: at least 21 days must have elapsed from infusion of last dose of antibody.\n  * Interleukins, interferons, and cytokines: at least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines.\n  * Stem cell infusions: at least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion.\n  * Cellular therapy: at least 42 days must have elapsed since the completion of any type of cellular therapy\n  * Radiotherapy (XRT): at least 1 month must have elapsed after local XRT.\n  * Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for at least 1 week.\n* Subject able to give consent\n\nExclusion Criteria:\n\n* Subjects that have previously received etoposide therapy\n* Subjects unable to tolerate study procedures and\u002For anesthesia based on the opinion of the principal investigator\n* Uncontrolled seizure disorder\n* Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities; a pregnancy test must be obtained in girls who are post-menarchal. Males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraception (e.g., a male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 month following their last study treatment requirement. Abstinence is an acceptable method of birth control. Women of childbearing potential will be provided a routine quantitative beta-human chorionic gonadotropin (B-hCG) test during the pre-study phase, prior to enrollment and each cycle.\n* Concomitant medications: subjects who are currently receiving another investigational drug or other anti-cancer agents are not eligible.\n* Screening EKG with a QTc \\> 450 msec.\n* Subjects with evidence of active systemic infection\n* Subjects with a documented allergy to compounds of similar chemical or biologic composition to etoposide or gadolinium compounds\n* Subjects with implanted metallic or electrical devices\n* Subjects with uncontrollable hypertension\n* Subjects with a documented bleeding disorder\n* Subjects with history of structural cardiac anomalies or arrhythmias\n* Subjects with history of unprovoked stroke or signs of stroke in the area of FUS target\n* Subjects with SARS-CoV-2 infection requiring hospitalization in the past month and requires anticoagulation as per the Columbia University Irving Medical Center (CUIMC) institutional \"Anticoagulation for COVID-19 Positive Pediatric Inpatients\" guidelines (See Appendix B)\n* Subjects with coagulopathy or under anticoagulant therapy.\n* Subjects with signs of impending herniation or an acute or previous intratumoral hemorrhage\n* Subjects with spinal cord diffuse midline glioma\n* Subjects receiving a drug where CNS toxicity is reasonably suspected","4 Years",{"count":142,"type":22},[168],"The blood brain barrier (BBB) prevents some drugs from successfully reaching the target tumor. Focused Ultrasound (FUS) using microbubbles and neuro-navigator controlled sonication is a non-invasive method of temporarily opening up the blood brain barrier to allow a greater concentration of the drug to reach into the brain tumor. This may improve response and may also reduce system side effects in the patient.\n\nThe primary purpose of this study is to evaluate the feasibility of safely opening the blood brain barrier in children with progressive diffuse midline gliomas (DMG) treated with oral etoposide using focused ultrasound with microbubbles and neuro-navigator-controlled sonication.\n\nFor the purpose of the study, the investigators will be opening up the blood brain barrier temporarily in one or two locations around the tumor using the non-invasive focused ultrasound technology, and administrating oral etoposide in children with progressive diffuse midline glioma.",[28,29],[287,288,289,290,291,200,203,292,293,294,295,296,28,297],"bood brain barrier","diffuse midline glioma","focused ultrasound","pontine glioma","thalamic glioma","Glioma","Brain Diseases","Nervous System Neoplasms","Central Nervous System Neoplasm","Etoposide","Brain Neoplasms","2026-01-26",{"date":266,"type":38},{"date":301,"type":38},"2023-06-05",{"date":303,"type":22},"2027-12",{"name":305,"class":45},"Columbia University",{"id":307,"slug":308,"hasResults":11,"nctId":309,"briefTitle":310,"officialTitle":311,"acronym":4,"eligibilityCriteria":312,"healthyVolunteers":11,"sex":17,"minAge":313,"maxAge":4,"enrollmentInfo":314,"targetDuration":4,"studyType":23,"phases":316,"briefSummary":317,"conditions":318,"keywords":319,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":322,"lastUpdatePostDateStruct":323,"startDateStruct":325,"completionDateStruct":327,"leadSponsor":329,"locationsCount":331},"100445230","phase-2-stereotactic-biopsy-split-course-radiation-therapy-in-diffuse-midline-glioma-sport-dmg-study-100445230","NCT05077735","Stereotactic Biopsy Split-Course Radiation Therapy in Diffuse Midline Glioma, SPORT-DMG Study","Stereotactic Biopsy Split-Course Radiation Therapy - Diffuse Midline Glioma (SPORT-DMG)","Inclusion Criteria:\n\n* Age \\>= 1 year(s) old (no maximum age)\n* Radiologic appearance of diffuse midline glioma of the pons, including diffuse infiltration of \\>= 50% of the pons on MRI, with or without extension to the midbrain and\u002For medulla oblongata with at least 1 of the 3 brainstem symptoms (cranial nerve deficit, long tract sign, or cerebellar sign)\n\n  * If all features of this clinicoradiologic criteria are met, then patients can continue on protocol with or without a biopsy\n  * If all features of this clinicoradiologic criteria are not met, patients must receive a brainstem lesion biopsy to be treated on protocol. If this cannot be completed, patients will be withdrawn from the study\n  * If biopsy has already been completed at an outside institution, the outside pathology report will be reviewed ahead of trial enrollment. The pathology specimen will then be sent to Mayo Clinic for further review, but will not delay study enrollment\n* Able to undergo MRI Brain\n* Negative urine pregnancy test completed =\\\u003C 7 days prior to registration, for women of childbearing potential only\n* Primary language of English or Spanish for patients and their caregiver\n* Patient or caregiver willing and able to provide written informed consent\n* Caregiver able to complete questionnaires by themselves or with assistance\n* Willing to return to enrolling institution for follow-up during the active monitoring phase of the study\n\nExclusion Criteria:\n\n* Any patient who has received previous radiation to the brain\n* Any patient who has received previous chemotherapy\n* Any patient with a diagnosis of neurofibromatosis type 1 or 2 (NF1 or NF2)\n* Any of the following:\n\n  * Pregnant women\n  * Nursing women\n  * Women of childbearing potential who are unwilling to employ adequate contraception\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Other active malignancy =\\\u003C 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix\n\n  * NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer\n* Patients \\> 16 years with an Eastern Cooperative Oncology Group (ECOG) score \\>= 4 and patients =\\\u003C 16 years with a Lansky play scale =\\\u003C 20","1 Year",{"count":315,"type":22},29,[25],"This phase II trial studies the clinical outcomes of hypofractionated radiation therapy in patients with diffuse midline gliomas. This study aims to change the way radiation is delivered, from giving 6 weeks of radiation all at once to giving 2 weeks of radiation. This may determine if there is a difference in the outcome of the treatment, and most importantly, the patients' quality of life.",[29],[200,320,203,321],"H3K27M","Diffuse Midline Glioma","2026-01-15",{"date":324,"type":38},"2026-01-20",{"date":326,"type":38},"2021-10-11",{"date":328,"type":22},"2027-10-15",{"name":330,"class":45},"Mayo Clinic",2,{"id":333,"slug":334,"hasResults":11,"nctId":335,"briefTitle":336,"officialTitle":337,"acronym":4,"eligibilityCriteria":338,"healthyVolunteers":11,"sex":17,"minAge":339,"maxAge":139,"enrollmentInfo":340,"targetDuration":4,"studyType":23,"phases":342,"briefSummary":343,"conditions":344,"keywords":351,"overallStatus":265,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":366,"startDateStruct":368,"completionDateStruct":370,"leadSponsor":372,"locationsCount":4},"100543554","phase-1-a-study-of-the-safety-dosing-and-delivery-of-neo100-in-patients-with-pediatric-brain-tumors-100543554","NCT06357377","A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors","An Open Label, Phase 1b Safety, Dose-finding, Brain Tumor Delivery, and Pharmacokinetics Study of Intranasal NEO100 in Patients With Pediatric-type Select Brain Tumors","Inclusion Criteria:\n\n* Patient must have radiographically confirmed, newly diagnosed or recurrent pediatric-type high grade glioma: Diffuse Midline Glioma, H3 K27-altered; Diffuse hemispheric glioma, H3 G34-mutant, Diffuse pediatric-type HGG, grade III and IV H3-wildtype and IDH-wildtype with imaging and\u002For pathology consistent with a DMG, (including spinal cord tumors); or Recurrent malignant tumors involving the brainstem or posterior fossa (choroid plexus carcinoma, CNS embryonal tumors, and pineoblastoma).\n* Karnofsky ≥ 50 for patients \\> 16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n* If clinically indicated, participants must be willing to provide adequate tissue for PK analysis, either from a surgical biopsy or needle biopsy.\n* Aged ≥5 to ≤18 years.\n* Patients recurrent or progressive disease must have recovered from all acute side effects of prior therapy.\n* From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibodies, or 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies.\n* Prior use of temozolomide during radiation at maximum of the standard pediatric dosing (defined as 90 mg\u002Fm2 \u002Fdose continuously during radiation therapy for 42 days) or dexamethasone is allowed.\n* Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 3 days prior to baseline magnetic resonance imaging (MRI) scan.\n* Surgical Resection: Patients may not have had a surgical resection within four weeks of starting NEO100 and any post-surgical complications must have resolved prior to initiation of NEO100.\n* Radiation Therapy: Patients may not receive radiation therapy within four weeks of starting NEO100. Patients may not be enrolled if they require radiation therapy during Cycle 1 (the DLT Period). Patients may have SOC radiation therapy in Cycle 2 or beyond but will require a second DLT evaluation period to participate.\n* Peripheral absolute neutrophil count (ANC) ≥ 1000\u002Fmm\\^3 (1.0g\u002Fl) AND\n* Platelet count ≥ 100,000\u002Fmm\\^3 (100x10\\^9\u002Fl) (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL\u002Fmin\u002F1.73 m\\^2.\n* Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age.\n* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase (ALT)) ≤ 2 x ULN.\n* Serum albumin ≥ 2 g\u002FdL.\n* No or mild renal impairment (i.e., 60 mL\u002Fmin or 1.73m2 with Schwartz equation).\n* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry of \\> 92% while breathing room air.\n* Participants with seizure disorder may be enrolled if seizure disorder is well controlled.\n* The effects of the study drugs on the developing human fetus are unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception. Adequate methods include: hormonal or barrier method of birth control; or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation.\n* A legal parent\u002Fguardian and patient must be able to understand, and willing to sign, a written informed consent (parental permission) or assent document, as appropriate.\n\nExclusion Criteria:\n\n* Diagnosis of any pediatric-type glioma not described in inclusion criteria.\n* Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy\u002Fresection should be discussed with the Medical Monitors.\n* Participants who are currently receiving other anti-cancer agents.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the Medical Monitor.\n* A marked baseline prolongation of QT\u002FQTc interval (e.g., repeated demonstration of a QTc interval \\>450 milliseconds (ms).\n* A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or the use of concomitant medications that prolong the QT\u002FQTc interval.\n* Participants with uncontrolled infection or other uncontrolled systemic illness.\n* Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy (as clinically indicated).\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in study.\n* Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of CSF dissemination as determined based upon available clinical details and not a study required MRI study or CSF test.\n* Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug.\n* Concomitant use of potent CYP3A4\u002F5 inhibitors during the treatment phase of the study and within 72 hours prior to starting study drug administration.\n* Concomitant use of potent CYP3A4\u002F5 inducers, which include enzyme inducing antiepileptic drugs (EIAEDs), during the treatment phase of the study and within 2 weeks prior to starting treatment. Concurrent corticosteroids are allowed.","5 Years",{"count":341,"type":22},12,[168],"This is an open label, Phase 1b safety, dose-finding, brain tumor delivery, and pharmacokinetics study of intranasal NEO100 in patients with pediatric-type diffuse high grade gliomas. Patients will receive IN NEO100 that will follow a dose titration design, followed by a standard dose escalation design to establish safety. Brain tumor delivery of NEO100 will be confirmed in each disease sub-type by surgical resection\u002Fneedle biopsy only if clinically indicated and scheduled for clinical purposes and testing with residual tissue for NEO100 and the major metabolite of NEO100 (Perillic Acid).",[345,346,29,347,348,349,350,60],"Pediatric Tumor of CNS","Pediatric Tumor of Brain","Pediatric Tumor of Brain Stem","Pineocytoma","Choroid Plexus Carcinoma, Childhood","Spinal Cord Tumor",[202,321,352,353,354,355,356,357,358,359,360,361,362,363,364],"H3 K27-altered","Diffuse hemispheric glioma","H3 G34-mutant","Diffuse pediatric-type HGG","H3-wildtype","IDH-wildtype","spinal cord tumors","Brainstem","Posterior fossa","Choroid plexus carcinoma","CNS embryonal tumors","Pineoblastoma","NEO100","2026-01-13",{"date":367,"type":38},"2026-01-14",{"date":369,"type":22},"2026-01",{"date":371,"type":22},"2026-10",{"name":373,"class":85},"Neonc Technologies, Inc.",{"id":375,"slug":376,"hasResults":11,"nctId":377,"briefTitle":378,"officialTitle":379,"acronym":4,"eligibilityCriteria":380,"healthyVolunteers":11,"sex":17,"minAge":139,"maxAge":4,"enrollmentInfo":381,"targetDuration":4,"studyType":23,"phases":383,"briefSummary":384,"conditions":385,"keywords":402,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":403,"lastUpdatePostDateStruct":404,"startDateStruct":406,"completionDateStruct":408,"leadSponsor":410,"locationsCount":156},"100404034","phase-1-phase-i-study-of-oral-onc206-in-recurrent-and-rare-primary-central-nervous-system-neoplasms-100404034","NCT04541082","Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms","A First-in-human Phase I Single-agent Dose-escalation, Food Effect and Dose Expansion Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms","Inclusion Criteria:\n\nPatients must meet all the following criteria to participate in the study:\n\n1. Patients aged ≥18 years with a recurrent, primary CNS neoplasm. For all cohorts, patients must have a histologically confirmed primary CNS neoplasm. Primary CNS neoplasms in this study include, but are not limited to, the following: glioblastoma and glioblastoma histologic subtypes, gliosarcoma, primary CNS sarcomas, anaplastic glial neoplasms including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed neuronal-glial tumors, and pilocytic astrocytoma with anaplastic features, diffuse astrocytoma, oligodendroglioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, diffuse midline gliomas and histone mutated gliomas (NOTE: Patients with H3 K27M-mutant diffuse gliomas are excluded unless the primary tumor is located in the pons or spinal cord, or the patient has completed front line radiation or received ONC201 therapy prior to 01 January 2023), ependymoma, anaplastic ependymoma, and all ependymoma subtypes, medulloblastoma and all medulloblastoma subtypes, atypical teratoid\u002Frhabdoid tumor, primary CNS embryonal\u002Fprimitive neuroectodermal tumors, atypical and anaplastic meningiomas, choroid plexus tumors, and pineal region tumors.\n2. Patients must have recurrent and measurable disease as defined by RANO criteria, using either the HGG and\u002For LGG RANO criteria based on tumor type, after having received established standard of care treatment for their disease and have no standard treatment options available as determined by the investigators. There is no limit on the number of total recurrences or prior therapies. However, prior therapies with known clinical benefit (including radiation) for specific tumor types are required. If patients are deemed ineligible for such therapies in the opinion of the Investigator, the Investigator must document the reason the patient is considered ineligible.\n3. Patients must have a Karnofsky Performance Score (KPS) of greater than or equal to 70. Patients with severe paraparesis\u002Fparaplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be considered eligible.\n4. (Inclusion Criterion #4 was removed in Amendment 3.)\n5. Patients must not have received prior investigational or approved cytotoxic chemotherapy within 28 days prior to the first dose of study drug (Cycle 1, Day 1); 42 days in the case of nitrosoureas; 42 days in the case of bevacizumab; 28 days or 5 half-lives (whichever is less; but not less than 14 days) in case of investigational or approved molecularly targeted agent; 14 days in the case of radiotherapy.\n6. (Inclusion Criterion #6 was removed in Amendment 7.)\n7. Patients with AEs Grade ≥2 related to prior therapies (chemotherapy, radiotherapy, and\u002For surgery) must have all their AEs resolved prior to the first dose of study drug (Cycle 1, Day 1), except for alopecia or neuropathy; Grade 1 or 2 lymphopenia is allowed.\n8. Patients must not have undergone major surgery 4 weeks prior to the first dose of study drug (Cycle 1, Day 1) and must have completely recovered from any surgery (minor surgical procedures such as skin biopsies and port placement done on an outpatient basis do not require a waiting period).\n9. Patients must have normal organ and marrow function as defined below:\n\n   * Absolute neutrophil count (ANC) ≥1,500\u002FmcL.\n   * Platelets ≥100,000\u002FmcL.\n   * Hemoglobin ≥9.0 mg\u002FdL without transfusion in 2 prior weeks.\n   * Total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome may be included with total bilirubin \\>1.5 × ULN if direct bilirubin is ≤1.5 × ULN).\n   * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × ULN.\n   * Measured or estimated creatinine clearance (CLcr) ≥40 mL\u002Fminute for patients with creatinine levels above normal. CLcr will be calculated by the Cockcroft-Gault equation for renal function.\n10. (Inclusion Criterion #10 was removed in Amendment 3)\n11. Patients must provide a tumor specimen (paraffin-embedded block and\u002For frozen tissue) from a prior resection or biopsy available that is sufficient to perform biomarker assays, ≥15 unstained slides for immunohistochemistry (IHC) analysis must be received by the NOB by the first dose of study drug (Cycle 1, Day 1). For patients with ≥10 to \\\u003C15 slides, eligibility will be reviewed on a case-by-case basis.\n12. Dependent upon dose level assignment and drug formulation (i.e., capsules versus powder in bottle \\[PIB\\]), patients must be able to either swallow oral capsules or swallow liquids.\n13. Patients must provide study-specific informed consent prior to enrollment. No Durable Power of Attorney or Next of Kin can provide initial consent.\n14. Patients must be able to tolerate a magnetic resonance imaging (MRI) study with intravenous gadolinium contrast.\n15. (Inclusion Criterion #15 was removed in Amendment 6)\n16. Patients must have a negative COVID-19 test within 72 hours of the first dose of study drug (Cycle 1, Day 1). Patients who had documented COVID-19 infection within 90 days of treatment but more than 20 days from infection do not need to be tested.\n17. (Inclusion Criterion #17 was removed in Amendment 6)\n\nExclusion Criteria:\n\nPatients who meet any of the following criteria will be excluded from the study:\n\n1. (Exclusion Criterion #1 was removed in Amendment 3)\n2. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206 (e.g., ONC201) or its excipients.\n3. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n4. Patients who are unable or unwilling to abide by the study protocol or cooperate fully with the Investigator.\n5. Patients with a known HIV-positive test on combination anti-retroviral therapy are ineligible for this initial first-in-human trial because of the potential for PK interactions with ONC206.\n6. Patients with active cardiac disease, including any of the following:\n\n   * Corrected QT interval (QTc) ≥470 msec on screening electrocardiogram (ECG; using the QTc by Fridericia's \\[QTcF\\] formula);\n   * Angina pectoris that requires the use of anti-anginal medication;\n   * Ventricular arrhythmias except for benign premature ventricular contractions;\n   * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;\n   * Conduction abnormality requiring a pacemaker;\n   * Valvular disease with documented compromise in cardiac function; and\u002For\n   * Symptomatic pericarditis.\n7. Patients with a history of cardiac dysfunction including any of the following:\n\n   * Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function;\n   * History of documented congestive heart failure (New York Heart Association functional classification III-IV); and\u002For\n   * Documented cardiomyopathy.\n8. Patients who have had an ischemic or hemorrhagic stroke in the last 3 months. If the patient has had a recent tumor resection, cerebral ischemic or hemorrhagic changes that occur peri operatively are not an exclusion.\n9. Patients with refractory epilepsy are excluded. Patients with primarily or secondarily generalized seizures in the 28 days prior to study enrollment will be excluded. Peri-operative seizures, defined as seizures occurring within the 7 days after a stereotactic biopsy, open biopsy, or surgical resection will not be an exclusion as long as the patient has had no generalized seizures starting 8 days after the surgical procedure. Patients with prior seizures must be on stable doses of 1 or 2 seizure medications for at least 14 days prior to study enrollment.\n10. Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ONC206 (uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).\n11. Patients who have been treated with any hematopoietic colony-stimulating growth factors (CSFs) (e.g., granulocyte-CSF, granulocyte-macrophage-CSF) ≤2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued.\n12. Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin derivative anticoagulant.\n13. Patients who are taking strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, 2D6, 1A2, 2C9, and 2C19 within at least 14 days prior to the first dose of study drug (Cycle 1, Day 1); these medications are excluded throughout the study.\n14. Women who are pregnant or breast feeding.\n15. Women of child-bearing potential with a positive serum pregnancy test ≤72 hours prior to the first dose of study drug (Cycle 1, Day 1).\n16. Patients who are receiving concomitant standard and\u002For investigational anti-cancer therapy.\n17. Patients with alcohol or substance abuse which, in the opinion of the Investigator, would interfere with compliance or safety.\n18. Patients with the presence of any other serious and\u002For unstable pre-existing medical disorder, psychiatric disorder, or other conditions that could interfere with patients' safety, obtaining informed consent or compliance to the study procedures as determined by the Investigators.\n19. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, or men who do not agree to use highly effective contraception during treatment and for 16 additional weeks after the final dose of study drug.\n\n    Highly effective contraception is defined as either:\n    * True abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\n    * Sterilization: Females must have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.\n    * Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.\n    * If patients are not practicing true abstinence and\u002For if the patient or sexual partner have not had a sterilization procedure as listed above, patients and their sexual partners must follow double barrier contraception in accordance with the guidelines for contraception below:\n\n      * Females of childbearing potential:\n\n        * Must use an intrauterine device or intrauterine system, during dosing of any study agent and for 16 weeks after final dose of study drug; or\n        * Must use a double barrier method of contraception: use of an occlusive cap (diaphragm or cervical\u002Fvault cap) with spermicide for women combined with use of a condom by their male partners capable of conceiving offspring.\n      * Males capable of conceiving offspring must use condoms during dosing of study agent and for an additional 16 weeks after final dose of study drug.\n\n    Note: Oral, implantable, or injectable contraceptives may be affected by CYP interactions, and are therefore not considered effective for this study.\n20. Previous receipt of ONC201, placebo, or blinded study drug from an ONC201 clinical study, or from any other source for H3 K27M-mutant diffuse glioma on or after 01 January 2023.",{"count":382,"type":22},102,[168],"The primary objective of this Phase 1, open-label, dose-escalation, and exploratory study is to evaluate the safety and tolerability profile (establish the maximum-tolerated dose) and evaluate the occurrence of dose-limiting toxicities (DLTs) following single weekly or multiple-day weekly dose regimens of single-agent, oral ONC206 in patients with recurrent, primary central nervous system (CNS) neoplasms.",[171,101,386,387,100,388,75,389,390,391,29,173,392,174,393,394,395,396,397,398,399,400,401],"Gliosarcoma, Adult","Anaplastic Oligodendroglioma","Pilocytic Astrocytoma","Gliomatosis Cerebri","Pleomorphic Xanthoastrocytoma","Anaplastic Pleomorphic Xanthoastrocytoma","Ependymoma, Anaplastic","Teratoid Rhabdoid Tumor","Neuroectodermal Tumors, Primitive","Neuroectodermal Tumors","Anaplastic Meningioma","Atypical Meningioma","Choroid Plexus Neoplasms","Pineal Tumor","Diffuse Astrocytoma","Glial Tumor",[101,100,387,400,75],"2025-12-17",{"date":405,"type":38},"2025-12-18",{"date":407,"type":38},"2020-10-26",{"date":409,"type":22},"2026-12",{"name":411,"class":85},"Jazz Pharmaceuticals",{"id":413,"slug":414,"hasResults":11,"nctId":415,"briefTitle":416,"officialTitle":417,"acronym":4,"eligibilityCriteria":418,"healthyVolunteers":11,"sex":17,"minAge":139,"maxAge":4,"enrollmentInfo":419,"targetDuration":421,"studyType":97,"phases":4,"briefSummary":422,"conditions":423,"keywords":433,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":441,"lastUpdatePostDateStruct":442,"startDateStruct":443,"completionDateStruct":445,"leadSponsor":447,"locationsCount":450},"100459206","observational-study-for-assessing-treatment-and-outcome-of-patients-with-primary-brain-tumours-using-cimpact-now-and-2021-who-classification-100459206","NCT05259605","Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Using cIMPACT-NOW and 2021 WHO Classification","Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Diagnosed According to cIMPACT-NOW Recommendations and the 2021 WHO Classification","* Age ≥ legal age of consent\n* Newly diagnosed or recurrent primary brain tumours within one of the 17 cohorts of interest\n* Archival tumour tissue from primary tumour available at the site. Representative tissue from first surgery is preferred, but tissue from surgery for recurrence is allowed. Exception: only tissue from first surgery is allowed for Cohort 16.\n* Available MRI\u002FCT scans from primary brain tumour at initial diagnosis\n* Patient's consent\n\nDeceased patient:\n\nThe clinical data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images can be accessed and used if at least one of the following three conditions is met:\n\n* The patient agreed beforehand in his\u002Fher lifetime to a further use of his\u002Fher data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images, or,\n* There is consent of a relative to use data and\u002For biological material and\u002For CT\u002FMRI\u002FPET images of the deceased patient, or,\n* There is a reference to a corresponding legal declaration covering the exemption in case of the impossibility or disproportion of getting access to an informed consent (e.g., causing strain on relatives of deceased patients).\n\nAdditionally, in all cases the following three points need to be fulfilled:\n\n* No documentation of previous objection of the patient to the (re-)use of their data, biological material, CT\u002FMR\u002FPET images for research purposes\n* A notification to an ethics committee for the re-use of these data, biological material and CT\u002FMRI\u002FPET images\n* Any other national requirements are fulfilled, if applicable",{"count":420,"type":22},1650,"10 Years","Every new classification depends on its prognostic power and on the type of treatment given. With the rapid evolution of diagnostic methods and the advance in new treatments, there is much less reliable information available on how patients with newly defined brain tumour entities should be treated and what to expect from the current treatments.\n\nThe goal is to determine whether the new 2021 WHO classification, based on cIMPACT-NOW recommendations, results in more homogeneous patient groups than the old 2016 classification. Furthermore, it will help derive provisional guidelines on how patients with these newly defined tumour entities are best treated. These recommendations will be based on the experience of EORTC investigators with chosen treatments and their experience as reported in this data collection report.",[292,424,425,426,427,428,29,173,429,399,430,431,432],"Glioneuronal Tumor","Choroid Plexus Tumor","Pineal Tumors","Germ Cell Tumor","Tumor of the Sellar Region","Embryonal Tumor","Hemangiopericytoma","Hemangioblastoma","Melanocytic Tumor of CNS",[434,435,436,437,438,439,440],"Rare primary brain tumor","2021 WHO Classification","molecular diagnosis","Gliomas","Choroid plexus tumors","Embryonal tumors","Pineal tumors","2025-12-11",{"date":403,"type":38},{"date":444,"type":38},"2023-03-21",{"date":446,"type":22},"2038-07-29",{"name":448,"class":449},"European Organisation for Research and Treatment of Cancer - EORTC","NETWORK",42,{"id":452,"slug":453,"hasResults":11,"nctId":454,"briefTitle":455,"officialTitle":455,"acronym":4,"eligibilityCriteria":456,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":457,"targetDuration":4,"studyType":97,"phases":4,"briefSummary":459,"conditions":460,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":461,"lastUpdatePostDateStruct":462,"startDateStruct":464,"completionDateStruct":466,"leadSponsor":468,"locationsCount":156},"100293588","international-diffuse-intrinsic-pontine-glioma-dipgdiffuse-midline-glioma-dmg-registry-and-repository-100293588","NCT03101813","International Diffuse Intrinsic Pontine Glioma (DIPG)\u002FDiffuse Midline Glioma (DMG) Registry and Repository","Inclusion Criteria:\n\n* All patients of any age (living or deceased) with a diagnosis (either current or past) of a DIPG\u002FDMG tumor\n* Unless the patient is deceased, all patients and\u002For one parent or legal guardian must provide written informed consent as well as HIPAA\u002Frelease of information consent.",{"count":458,"type":22},1500,"Doctors and other medical scientists want learn about the biology of DIPG\u002FDMG and to develop better ways to diagnose and treat patients with DIPG\u002FDMG. To do this, they need more information about the characteristics of DIPG\u002FDMG tumors. Therefore, they want to establish a central location for clinical information and tumor tissue collected from DIPG\u002FDMG patients.\n\nThe purposes of this study are:\n\n* To enroll patients diagnosed with DIPG\u002FDMG in the International DIPG\u002FDMG Registry and Repository.\n* To provide a central location for clinical information, scans, and tissue samples from patients with DIPG\u002FDMG enrolled in the registry.\n* To collect tissue samples in order to study how DIPG\u002FDMG works on the molecular level. Researchers may use the tissue samples to study molecules such as proteins and DNA. Proteins are needed for the body to function properly and DNA is the molecule that carries our genetic information. Other researchers will be able to use the stored samples in the future to learn more about DIPG\u002FDMG. The information researchers get from the research studies will be kept in the registry along with the clinical information.\n* To help investigators around the world to work together to make more consistent diagnosis and better design of future research studies. We hope this will lead to better treatments for DIPG\u002FDMG in the future.",[28,29,321],"2025-10-16",{"date":463,"type":38},"2025-10-20",{"date":465,"type":38},"2012-06",{"date":467,"type":22},"2047-06",{"name":469,"class":45},"Children's Hospital Medical Center, Cincinnati",{"id":471,"slug":472,"hasResults":11,"nctId":473,"briefTitle":474,"officialTitle":474,"acronym":475,"eligibilityCriteria":476,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":477,"enrollmentInfo":478,"targetDuration":4,"studyType":23,"phases":480,"briefSummary":481,"conditions":482,"keywords":483,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":486,"lastUpdatePostDateStruct":487,"startDateStruct":489,"completionDateStruct":491,"leadSponsor":493,"locationsCount":331},"100564069","phase-1-atovaquone-combined-with-radiation-in-children-with-malignant-brain-tumors-100564069","NCT06624371","Atovaquone Combined With Radiation in Children With Malignant Brain Tumors","AflacBT2303","Inclusion Criteria:\n\n-Stratum 1\n\n* Newly diagnosed pHGG\u002FDMG\u002FDIPG Patients must have histologically confirmed pediatric high-grade glioma (pHGG, WHO Grade 3 or 4) or diffuse midline glioma with altered H3K27 (DMG, WHO Grade 4). Primary pHGG or DMG spinal tumors are eligible. Diffuse intrinsic pontine glioma (DIPG) defined by MRI does not require histological confirmation.\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Adequate liver function defined as:\n\n  * Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  * AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n* Patients must have normal organ and marrow function as defined below:\n\n  * absolute neutrophil count \\> 1,000\u002FmcL\n  * platelets \\> 100,000\u002FmcL\n  * hemoglobin \\> 8g\u002FdL\n  * Total bilirubin within normal institutional limits\n  * AST(SGOT)\u002FALT(SGPT) \\\u003C 5 x (\\\u003C10 x if taking steroids) the institutional upper limit of normal\n  * creatinine within normal institutional limits for age 2 OR\n  * creatinine clearance \\> 60mL\u002Fmin\u002F1.73 m for patients with creatinine levels above institutional normal\n\nStratum 2\n\n* Relapsed, progressive pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of standard radiation therapy without prior atovaquone exposure and before progression. Patients with metastatic disease are allowed for Stratum 2 only.\n\n  --Measurable disease is not necessary for enrollment study.\n* Patients must have previously undergone standard-of-care treatment including surgery, radiation, and\u002For first-line adjuvant chemotherapy before the experimental treatment (atovaquone).\n* Patients must have recovered from the acute treatment-related toxicities (defined as \\\u003C grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed.\n* Age \\> 2 to 25 years\n* Weight \\> 10kg\n* Karnofsky and Lansky performance score \\> 50%\n* Patients with stable seizures (e.g., no seizures for ≥ 7 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible.\n* Patients must have normal organ and marrow function as defined above for Stratum 1\n* Adequate liver function is defined as:\n\n  1. Total bilirubin ≤ 2x upper limit of normal (ULN) and\n  2. AST (SGOT) and ALT (SGPT) ≤ 225 U\u002FL (5x the ULN). The ULN for AST and ALT will be 45 U\u002FL.\n\nExclusion Criteria:\n\nStratum 1\n\n* Chronic systemic concurrent illness\n* Concurrent or history of anti-cancer therapy other than RT\n* Patients with metastatic tumor are excluded for Stratum 1 only.\n* Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Symptomatic intratumoral hemorrhage, or asymptomatic intratumoral hemorrhage larger than punctate foci, at any time prior to enrollment.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.\n\nStratum 2\n\n* Concurrent illness\n* Patients must have recovered from all prior therapy as follows:\n\n  1. Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks before study enrollment or at least six (6) weeks if prior nitrosourea.\n  2. Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days before study enrollment.\n  3. Antibodies: ≥ 21 days must have elapsed from an infusion of the last dose of antibody and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed before enrollment.\n  4. Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days before enrollment.\n  5. Radiation: Patients must have had their last fraction of • Craniospinal irradiation ≥ 3 months before enrollment. • Other substantial bone marrow irradiation ≥ 6 weeks before enrollment • Local or palliative XRT (small port) ≥ 2 weeks.\n  6. Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow\u002Fstem cell transplant before enrollment. Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs are excluded.\n* Patients must fully recover from all acute effects of prior surgical intervention.\n* History of allergic reactions to atovaquone or attributed to compounds of similar chemical or biological composition to atovaquone.\n* Pregnant or breast-feeding women will not be entered into this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment. This should be documented in the electronic medical records as part of the consent discussion.","25 Years",{"count":479,"type":22},18,[168],"The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma\u002Fdiffuse midline glioma\u002Fdiffuse intrinsic pontine glioma (pHGG\u002FDMG\u002FDIPG).\n\nThe secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG\u002FDMG\u002FDIPG and medulloblastoma (MB) or pHGG\u002FDMG\u002FDIPG after completion of RT and before progression.",[263,174,28,29],[484,485],"Atovaquone","Progression-free survival","2025-07-21",{"date":488,"type":38},"2025-07-22",{"date":490,"type":38},"2025-03-28",{"date":492,"type":22},"2027-10",{"name":494,"class":45},"Emory University",{"id":496,"slug":497,"hasResults":11,"nctId":498,"briefTitle":499,"officialTitle":500,"acronym":4,"eligibilityCriteria":501,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":477,"enrollmentInfo":502,"targetDuration":4,"studyType":23,"phases":504,"briefSummary":505,"conditions":506,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":508,"lastUpdatePostDateStruct":509,"startDateStruct":511,"completionDateStruct":513,"leadSponsor":515,"locationsCount":156},"100539597","phase-1-cd200ar-l-and-allogeneic-tumor-lysate-vaccine-immunotherapy-for-recurrent-hgg-and-newly-diagnosed-dmgdipg-in-children-and-young-adults-100539597","NCT06305910","CD200AR-L and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent HGG and Newly Diagnosed DMG\u002FDIPG in Children and Young Adults","Phase I Trial: CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy With Adjuvant Reirradiation for Recurrent High-Grade Glioma and Newly Diagnosed Diffuse Midline Glioma\u002FDiffuse Intrinsic Pontine Glioma in Children and Young Adults","Inclusion Criteria:\n\n* Histologically confirmed newly diagnosed DIPG\u002FDMG with documented H3K27M alteration (based on IHC or DNA sequencing performed in a CLIA-certified laboratory) or recurrent HGG. Patients cannot enroll until they are a minimum of 14 days and preferably within 30 days from the last dose of radiation.\n* Diagnosis of recurrent HGG based on MRI findings. Recurrent HGG must have received standard of care radiation at diagnosis. Prior biopsy material will be required to confirm diagnosis of HGG; however, biopsy of the recurrent\u002Fprogressive lesion will not be required for study enrollment.\n* Maximal safe resection is preferred prior to clinical trial enrollment if indicated and feasible.\n* Clinically stable on a dose of corticosteroids not to exceed an equivalent of dexamethasone 0.1 mg\u002Fkg\u002Fday (maximum 4 mg) for at least 2 weeks prior to study enrollment.\n* Prior therapy wash-out is required\n* Minimum of 28 days since last dose of any targeted therapy (including bevacizumab), immunotherapy, investigational agents.\n* Minimum of 10 days since any anti-cancer intervention: cytoreductive surgery\u002Flaser ablation and a minimum of 28 days since any viral therapy\n* Voluntary written consent obtained by patient if ≥18 years of age or a parent or guardian if \\\u003C18 years of age before the performance of any study-related procedure not part of standard medical care\n* Able to comply with follow-up visit schedule (i.e., return to clinic for follow-up visits).\n* Willing to allow for collection of pre-treatment research related blood collection \\[1-5 mL red top tube and 2-10 mL green top tubes (or to a max of 2 ml\u002Fkg of body weight)\\] for immune characterization. If a patient does not subsequently enroll in the study, the samples will be destroyed according to institutional protocol.\n* Lansky play performance score ≥60 (\\\u003C16 years) or Karnofsky (≥16 years) performance score of ≥60\n* Sexually active persons of child-bearing potential or with partners of childbearing potential must agree to use a highly effective form of contraception during the 2-year treatment period. Urine pregnancy tests will be obtained at defined time points during protocol therapy.\n* Adequate bone marrow reserve: Absolute neutrophil (segmented and bands) count (ANC) ≥1.0 x 10E9\u002FL, platelets ≥75 x 10E9\u002FL; Hemoglobin ≥8 g\u002FdL\n* Hepatic: Bilirubin ≤1.3 mg\u002FdL and SGPT (ALT) ≤2.5 x upper limit of normal (ULN) for age\n* Renal: Normal serum creatinine for age or creatinine clearance \\>60 ml\u002Fmin\u002F1.73 mE2\n\nExclusion Criteria:\n\n* Known sensitivity to the GBM6-AD tumor lysate vaccine, CD200AR-L, or imiquimod.\n* Unable to complete a standard upfront course of radiotherapy due to disease progression or intolerance of therapy.\n* Radiographic evidence of diffuse leptomeningeal disease.\n* Prior history of malignancy within 5 years of enrollment.\n* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n* Concurrent use of tumor treatment field devices (e.g., Optune) - permitted until the time of consent.\n* History of any laboratory findings consistent with any uncontrolled immune system abnormalities such as hyper-immunity (e.g., autoimmune diseases, thyroid dysfunction, lupus, scleroderma, etc.) and hypo-immunity \\[e.g., myelodysplastic disorders, marrow failures, human immunodeficiency virus\u002Facquired immunodeficiency syndrome (HIV\u002FAIDS), transplant immune-suppression, etc.\\]. Any known autoimmune disease must be clinically silent and without associated laboratory abnormalities for at least 1 year in the absence of any disease directed therapy or systemic steroids.\n* Any conditions that could potentially alter immune function (e.g., HIV\u002FAIDS, hepatitis B, untreated hepatitis C, multiple sclerosis, renal failure).\n* Receiving ongoing treatment with any immunosuppressive drug for any reason, excluding those patients requiring a low dose of corticosteroids equivalent to dexamethasone 0.1 mg\u002Fkg\u002Fday (maximum 4 mg) or less for treatment of tumor-related edema.\n* Not able to tolerate an MRI or radiation therapy even with reasonable accommodations or sedation.\n* Known pregnancy or anticipated conception during the 1-year study period",{"count":503,"type":22},24,[168],"This is a single center Phase I study of a new adjuvant CD200 activation receptor ligand, CD200AR-L, in combination with imiquimod and GBM6-AD vaccine to treat malignant glioma in children and young adults.\n\nThe primary objective of this study is to determine the maximum tolerated dose (MTD) of CD200AR-L when given with a fixed dose of GBM6-AD vaccine, imiquimod, and a single dose of radiation for patients with recurrent High Grade Glioma (HGG) or following standard of care therapy radiation therapy for newly diagnosed Newly Diagnosed Diffuse Midline Glioma\u002FDiffuse Intrinsic Pontine Glioma (DIPG\u002FDMG).",[29,507],"Recurrent High Grade Glioma","2024-03-05",{"date":510,"type":38},"2024-03-12",{"date":512,"type":22},"2024-03-15",{"date":514,"type":22},"2027-01-15",{"name":516,"class":85},"OX2 Therapeutics",{"id":518,"slug":519,"hasResults":11,"nctId":520,"briefTitle":521,"officialTitle":521,"acronym":522,"eligibilityCriteria":523,"healthyVolunteers":11,"sex":17,"minAge":94,"maxAge":164,"enrollmentInfo":524,"targetDuration":4,"studyType":23,"phases":526,"briefSummary":528,"conditions":529,"keywords":4,"overallStatus":265,"whyStopped":4,"lastUpdateSubmitDate":534,"lastUpdatePostDateStruct":535,"startDateStruct":537,"completionDateStruct":539,"leadSponsor":541,"locationsCount":4},"100523249","re-irradiation-of-diffuse-midline-glioma-patients-100523249","NCT06093165","RE-irradiation of Diffuse MIdline Glioma paTients","REMIT","Inclusion Criteria:\n\n* Diffuse midline glioma diagnosis: verified radiologically or histologically Biopsy is not mandatory for REMIT\n* Age ≥ 12 months to ≤21 years.\n* Min. 180 days\u002F6 months have elapsed from the first day of the 1st RT course\n* 1st course of radiotherapy\n* Full recovery from all acute and subacute toxicities of 1st RT course\n* Clinical progression of symptoms and\u002For radiographic progression\n* Karnofsky performance status scale or Lansky Play Scale \\> 50% The performance status should not take the neurological deficits per se into account.\n\nNB: Children and adults with a worsening performance status due to glioma-related motor deficit can be included.\n\n* Life expectancy \\> 12 weeks after start of reRT\n* Signed informed consent by patient and\u002For parents or legal guardian\n\nExclusion Criteria:\n\n* Presence of leptomeningeal spread or multifocal disease on MRI at progression\n* Other co-morbidity that according to the treating physician would impair participation in the study\n* \\>1 course of radiotherapy\n* Neurofibromatosis type 1\n* Inability to complete the medical follow-up (geographic, social, or mental reasons)",{"count":525,"type":22},59,[527],"NA","The REMIT (RE-irradiation of diffuse MIdline glioma paTients) study evaluates safety and the palliative efficacy of re-irradiation of patients with diffuse midline glioma (DMG). The study will introduce a standard re-irradiation treatment schedule for DMG patients who have progressed following primary treatment.",[29,28,530,531,532,533],"Diffuse Glioma","Pontine Tumors","Thalamic Tumor","Brain Tumor, Pediatric","2023-10-16",{"date":536,"type":38},"2023-10-23",{"date":538,"type":22},"2023-10",{"date":540,"type":22},"2029-11",{"name":542,"class":45},"Rigshospitalet, Denmark",{"id":544,"slug":545,"hasResults":11,"nctId":546,"briefTitle":547,"officialTitle":548,"acronym":549,"eligibilityCriteria":550,"healthyVolunteers":11,"sex":17,"minAge":4,"maxAge":551,"enrollmentInfo":552,"targetDuration":4,"studyType":23,"phases":553,"briefSummary":554,"conditions":555,"keywords":556,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":558,"lastUpdatePostDateStruct":559,"startDateStruct":561,"completionDateStruct":563,"leadSponsor":565,"locationsCount":156},"100481094","phase-1-car-t-cells-to-target-gd2-for-dmg-100481094","NCT05544526","CAR T Cells to Target GD2 for DMG","Chimeric Antigen Receptor (CAR)-T Cells to Target GD2 for Diffuse Midline Glioma","CARMIGO","Inclusion Criteria:\n\n1. Age ≥ 2 and ≤ 16 years\n2. Tissue diagnosis of H3K27M mutant Diffuse Midline Glioma.\n3. Radiographically evident tumour restricted to the brain stem or spinal cord.\n4. At least 6 weeks following completion of radiation therapy.\n5. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial\n6. Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \\\u003C 10) score ≥ 40% allowing for stable neurological deficit due to DMG\n7. Absolute neutrophil count ≥1.5 x109\u002FL and platelet count ≥ 100 x109\u002FL\n8. Total bilirubin \\\u003C 1.5 ULN and ALT \\\u003C 2.5 ULN\n9. Serum creatine \\\u003C 1.5 ULN for age.\n10. For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable)\n11. Written informed consent\n\nExclusion Criteria:\n\n1. Systemic corticosteroid therapy ≥ 0.05 mg\u002Fkg dexamethasone daily (or equivalent) at time of RQR8\u002FhuK28Z CAR T cell infusion\n2. Tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed)\n3. Clinical or radiological evidence of true tumour progression\n4. Active hepatitis B, C or HIV infection\n5. Inability to tolerate leukapheresis\n6. Pre-existing significant neurological disorder not related to DMG\n7. Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.\n8. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC\n9. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution\n10. Any contraindication to Ommaya reservoir insertion (or similar catheter)\n11. Known allergy to albumin, DMSO or EDTA\n12. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression \u002Fsystemic disease modifying agents within the last 2 years\n13. Prior treatment with investigational or approved gene therapy or cell therapy products\n14. Life expectancy \\\u003C3 months\n15. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to RQR8\u002FhuK28Z CAR T cell infusion\n16. Post-pubertal subjects who are pregnant or breastfeeding","16 Years",{"count":341,"type":22},[168],"The CARMIGO Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in children and young adults aged 2-16 years with Diffuse Midline Glioma (DMG).\n\nThe study will evaluate the feasibility of generating the ATIMP, the safety and tolerability of the GD2CAR T-cell therapy and how effectively GD2CAR T-cells engraft, expand and persist following administration in patients with DMG.",[29],[557,321,203],"CAR T cells","2023-09-06",{"date":560,"type":38},"2023-09-11",{"date":562,"type":38},"2023-08-15",{"date":564,"type":22},"2039-12",{"name":566,"class":45},"University College, London"]